Monthly Archives: January 2013

The Connection Between Regenerating Deer Antlers and The PTHrP, PTH And IHH pathway for Cartilage Regulation, PTHrP Seems To Be The Answer (Big Breakthrough!)

When there is something critical that can push our research much further I really go deep into the material to learn what it means and this recent finding may be one of the biggest finds I have gotten in a while. It seems to be one of those studies that connects many of the subjects that the serious height increase researchers would have seen before and gives a few big ideas on how to possibly stimulate height increase. The implications which I would learn is quite immense.

Update 3/8/2013: In the 7th Natural Height Growth Podcast Episode with Tyler we have only briefly mentioned the fact that I was looking at this phenomenon of deer antler growth to possibly find general growth principles which shows why this mamaliam bone growth is possible. I have directed him to the study so he can see the type of research I was doing a few weeks ago. This post will go much deeper into the technical details. I will be dissecting the PubMed study below and then give a interpretation on how we can use the theory for height increase and how to grow taller.

From PubMed study…

Recapitulation of the parathyroid hormone-related peptide-Indian hedgehog pathway in the regenerating deer antler. (source link)

Abstract

C. Faucheux, B.M. Nicholls, S. Allen, J.A. Danks, M.A. Horton, and J.S. Price

deer antlerParathyroid hormone (PTH)-related peptide (PTHrP) and the PTH/PTHrP receptor (PPR) play an essential role in controlling growth plate development. The aim of the present study was to use the deer antler as a model to determine whether PTHrP and PPR may also have a function in regulating cartilage and bone regeneration in an adult mammal. Antlers are the only mammalian appendages that are able to undergo repeated cycles of regeneration, and their growth from a blastema involves a modified endochondral process. Immunohistochemistry was used to establish sites of localization of PTHrP and PPR in antlers at different stages of development. The pattern of Indian Hedgehog (IHH) and transforming growth factor-beta1 (TGF1) distribution was also investigated, because PTHrP expression in the developing limb is regulated by IHH and during embryonic growth plate formation TGF1 acts upstream of PTHrP to regulate the rate of chondrocyte differentiation. In the antler blastema (<10 days of development), PTHrP, PPR, and TGF1 were localized in epidermis, dermis, regenerating epithelium, and in mesenchymal cells but IHH expression was not detected. In the rapidly growing antler (weeks 4 – 8 of development), PTHrP, PPR, and TGF 1 were localized in skin, perichondrium, undifferentiated mesenchyme, recently differentiated chondrocytes, and in perivascular cells in cartilage but not in fully differentiated hyperytrophic chondrocytes. IHH was restricted to recently differentiated chondrocytes and to perivascular cells in cartilage. In mineralized cartilage and bone, PTHrP, PPR, IHH, and TGF1 were immunolocalized in perivascular cells and differentiated osteoblasts. PTHrP and PPR were also present in the periosteum. TGF1 in vitro stimulated PTHrP synthesis by cells from blastema, perichondrium, and cartilage. The findings of this study suggest that molecules which regulate embryonic skeletal development and postnatal epiphyseal growth may also control blastema formation, chondrogenesis, and bone formation in the regenerating deer antler. This finding is further evidence that developmental signaling pathways are recapitulated during adult mammalian bone regeneration. Developmental Dynamics 231:88 –97, 2004.

© 2004 Wiley-Liss, Inc. Received 28 August 2003; Revised 10 March 2004; Accepted 24 March 2004

Analysis & Interpretation of the Abstract:

The study the researchers did was to see whether the PTHrP/PPR pairs have  any type of regulation function on the cartilage and bone regeneration in adult mammals. Note: I would assume most of the people reading this post are adult mammals.

I had written before in a previous post about the possible that the Parathyroid Hormone related Peptide, the PTHrP being the possible compound that we should be focusing on increasing expression and concentration the most if we were to take a crack at finding a non-invasive, non limb-lengthening method. The post was “Parathyroid Hormone And Parathyroid Hormone-Related Protein May Lead To Non-Invasive Epiphyseal Growth Plate Regeneration (Big Breakthrough)” The idea from that post was that theire seemed to have been enough studies and articles published showing that the PTHrP can cause all the other growth factors and chondrogenic process to restart again to form more chondrocytes, thus cartilage, thus epiphyseal plates. Of course the connection between PTHrP expression, and overgrowth turning into cancer, still showed as Tyler pointed out that it might be the indian hedgehog, IHH, which seems to be regulating the PTHrP.

First, let’s look at the introduction. In the introduction, the writers give us a good introduction at seeing the analog and similarities between how deer antlers grow and how the human limb grows during the endochondral ossification process.

We look at 4 main growth factors or regulating factors.

  • Parathyroid Hormone related Protein, PTHrP
  • Indian Hedgehog, IHH, ihh
  • PTH/PTHrP receptor, PPR
  • Transforming Growth Factor Beta 1, TGFBeta1

The researchers have already done their research and read the more important studies which show how the PTHrP, IHH and others work together to regulate the process of endochondral ossification in the growth plate. It seems that for the deer antlers, they actually stop growing in length when the testosterone is increased up to a certain level. That to begin with is something that is noted maybe for later.

Others things to note is that the retinoic acid and its receptor will control how the growth plate behaves, as we have seen in previous studies and written about in previous posts.

The PTHrP itself does two main functions, stimulate chondrocyte proliferation, and inhibit the differentiation of chondrocytes. It also can regulate the differentiation of antler osteoclasts.

The PTHrP/PPR combo regulate chondrocyte differentiation. The indian hedgehog, IHH, can regulate the expression of the PTHrP. It is expressed in the prehypertrophic chondrocytes. Both the PTHrP and the IHH control differentiation of growth plates chondrocytes.

Not just the IHH, but also the TGFBeta-1 might also be a primary regulator of PTHrP. It has been found from immunohistological studies that the mRNA of the TGFBeta-1 has been found in antler tissues. The TGFBeta-1 acts upstream of PTHrP to regulate the rate of hypertrophic differentiation and also increase the PTHrP expression in osteoblasts.

Now let’s see the schematic on how the deer antler components are arranged. 

After the old antler is completely grown and reaches maximum length, it stops growing and falls off. The stump that is left over has a sort of wound in the center of the pedicle, which is the thing that juts out of the deer’s head. The wound after a few weeks somehow manages to form a blastema, and the blastema is what can grow. There are 2 main layers and 4 sub layers to the growing antler.

You have the antler skin, called the velvet, which breaks apart into two adjacent layers called the epidermis and the dermis.

You than have the perichondrium underneath the velvet, which has two layers as well, the outer layer which is more collagenous, and the inner layer which is filled with mesenchymal progenitor stem cells which have not been differentiated yet. These progenitor cells have not shown to express alkaline phosphatase yet so they are not chondrocytes in the hypertrophic stage. They are not expressing collagen Type II so they are not at the proliferation stage yet either. When the mesenchymal stem cells do finally manage to start differentiation ,somehow they manage to be able to do it in stacked columns, Between the chondrocytes are the vascular channels and the perivascular tissue which have osteoclast and osteoblast progenitor cells there already. The mesenchyme and the chondrocytes which form from it have cartilage like tissue below it and below that cartilage is the mineraliazed cartilage tissue.

Remember now, the researchers were looking at how the four main growth regulating factors were localized in the growing antler over time from the initialy deer antler falling off leading a fresh wound, through when the blastema forms, and when the blastema turns into something much bigger.

pthrp chartWhat we are finding if we review the chart to the right is that the PPR and the PTHrP seem to be localized in almost the same places during the blastema formation ,except that the PPR expression can’t be found in the layer of the perichondrium that is filled with blood vessels. The chart is very nicely displayed in showing how much the expression of PTHrP, PPR, TGFBeta-1, IHH, and Collagen X is  going on in each subjacent layer, from the outer epidermis, down to the bone.

Both the PTHrP and the PPR don’t seem to show expression in fully differentiated chondrocytes, which sort of validates the idea that maybe the PTHrP as well as the PPR being used in a way to reverse or at least inhibit complete cartilage to bone conversion.

The IHH has found in very recently differentaited chondrocytes but not found in fully differentiated chondrocytes. As for the TGFBeta-1, we saw that the TGFBeta-1 expression was similar to the PTHrP but at a lower level of concentration or intensity.

pthrp chart 2All 4 the ihh, the pthrp, tgfbeta-1 and the ppr call showed expression in at least the perivascular tissue between the chondrocytes and the osteoblasts in the perivascular tissue.  It might be a good idea for any serious height increase researcher to look over the chart.

The researchers wrote in the discussion section that …“PTHrP and IHH are “master regulators” of chondrocyte proliferation during endochondral bone formation and IHH also regulates osteoblast differentiation”

What may be the most insightful and the most important part to the study was the section…

“….proposed that antler regeneration represented a failure of scar formation, based on his observation that suturing the skin over the regenerating blastema inhibited antler development.”

This seems to suggest that everything we have been thinking about and assuming about how to grow taller may be completely wrong, and just the opposite. We see that the TGF-Beta1 expression is very low while the local expression of the PTHrP and the PPR are localized to the epithelium layer and the mesenchymal progenitor cell level. We know from so many other PubMed studies that the TGF-Beta1 is not just a osteogenic and a chondrogenic growth factor regulator, but that the process of chondrogeneis and osteogenesis suggest that the wound made from some type of fracture would be healed over. The researchers are proposing that the inhibition of deer antler stump wound closure is what actually allows the antlers to be ever formed in the first place.

The other big thing to note is that during the early blastema formation/ development stages the IHH expression is not found, but the PTHrP is found. This shows that at least for deer antler regeneration the IHH is not used as a regulator on PTHrP expression. This would agree with my proposed idea from the post “Parathyroid Hormone And Parathyroid Hormone-Related Protein May Lead To Non-Invasive Epiphyseal Growth Plate Regeneration (Big Breakthrough)“. The big thing that developed after writing that post was that we are not sure whether the IHH or the PTHrP was the more important growth factor for growth plate regulation. Like the researchers said, the PTHrP and the IHH are the two master regulators. Tyler has said that it seems that the IHH is what will regulate PTHrP but we also realize that the PTHrP-IHH is not a simple regulator-regulated relationship but a feedback loop system unit for analysis. This means that not only does the IHH regulate the PTHrP expression, but the PTHrP regulates the IHH expresson too.

So this thing turns into a feeback loop that regulates itself. So which one comes first, IHH or PTHrP? It is similar to the old chicken-egg paradox, as to which one came first. Which one is more important since it is what will be the original growth factor to start all the rest of the growth factors in a cascade to possibly regenerate cartilage again. I say that this study and article seems to validate and give more evidence towards the idea that the PTHrP is the compound with more important for our endeavor of height increase and to grow taller.

Of course this is not to take away the importance of the other 3 main compounds studied in this study. The researchers learned that the TGF-Beta1 can dramatically increased the expression of PTHrP.

Faucheux and Price (1999) stated that ” PTHrP does not appear to regulate proliferation of progenitor cells derived from perichondrium” this sort of puts a dent in our height increase ideas, since we can’t just use the PTHrP injected into perichondrium to stimulate the inner perichondrium layer cells to to through chondrogenesis and proliferate. What the writer seem to suggest is that the PTHrP is used to regulate proliferation of progenitor cells derived from the mesenchyme instead.

I quote the section from Discussion

However, once chondrogenesis is evident, it may maintain proliferation of chondroprogenitor cells, since our earlier in vitro observations showed that PTHrP inhibited differentiation but stimulated growth in chondrocyte micromass cultures (Faucheux and Price, 1999). The observation that there is no PTHrP in terminally differentiated, nonproliferating chondrocytes in the blastema would support this suggestion

So if we can just get the chondrogenetic process started with the right intial growth factor spark ,we can sustain the proliferation capacities of the few perichondrium cells using PTHrP. PTHrP is not doubt very important. What is interesting for the researchers and myself is that fact that the PTHrP expression was seen in the blood vessel layer of the perichondrium but the PTH/PTHrP receptor (or PPR) was not. The amazing thing for these regenerating deer antlers is that the PTHrP can regulate itself because the PPR expression was localized to the antler perichondrium nonvascularized region.

Implications For Height Increase

deer antlerWe are seeing that the PTHrP and its receptor the PPR are two of the most critical factors and they seem to be the key factor that separates the epiphyseal cartilage and the regenerating antlers found in deer.

Like with humans, the increase in some type of androgen, this time being the testosterone, is what will cause the longitudinal growth of the “bone” like material to stop. For humans, that was the androgen estrogen.

The few things we learn in this study has dramatically changed the way we view longitudinal bone growth. the thing that is most interesting is that we found out that what can probably help with bone fracture healing can actually inhibit bone length growth.

Let’s look at the diagram on the right and see where it is similar to a growth plate but is also different. This bone area which will eventually protrude from the antler stump has a specific growing pattern.

The blastema formed from the epithelial tissue and the wound made by the antler falling off is something I am not sure of yet.

You have the 2 layer perichondrium which will have the PHTrP and the PPR to start with. The IHH is not found in the perichondrium and the TGF-Beta1, while it would increase the PTHrP, is also low.

So you have the raw material first, the mesenchymal progenitor at the tip, surrounded by the perichondrium, and the skin layers, which are elastic. If you imagine how the growing process would go, it would be very similar to how the long bones grow longer. The top part does not move forward and leave the cartilage to be ossified later. It seems more like that the chondrocytes that are differentiated by the mesenchyme pushes themselves on top of each other, which would automatically result in a stacking columnar formation. The cells are aligned neatly in a one 2 dimensional plane. If they are to proliferate, the newly created chondrocytes would push down the old chondrocyte on top of the older chondrocytes. if then the chondrocytes can then expand in size, they can push each other further apart and widen the cartilage in the vertical direction, which is growing taller.

The thing is that as adult humans with closed epiphyseal plates, we still have the perichondrium, and the mesenchyme, which will be in random found in the trabecular bone matrix in the epiphysis ends of the long bones. Obviously we have the bones. What we don’t have are the cartilage. 

But do we need the cartilage to work?? No, the diagram on the right suggest that we might not need to have cartilage to do the transplant,, since the mesenchyme with the right growth factors will create the cartilage or at least the stacking chondrocytes automatically.

We could say that theoretically the core reason the regeneration of deer antler can even happen is because of the blastema, but a blastema is just a dense packing in maybe a certain order of undifferentiated pluripotent stem cells. we have that in the human adult in the epiphysis since the human marrow is usually what people ask to give up in some cancer treatments, but they are not that pure and only made up of say the cells, but also have a lot of bood vessels going through.

If we wanted to say change the concentration or distribution of the factors analyzed like PTHrP, PPR, TGF-Beta1, or IHH, we could theoretically inject through syringes certain areas of our body to get the increased or right amount of growth factor needed to increase height. Growth factors should not, and would not be the main contraint on why the deer antler can keep regrowing after each year, but the adult human epiphyseal growth plate can’t.

But now I don’t think we need the plates!. That”s right, I said it. At this point in the research, I don’t think we need to bring back the growth plates to grow taller. 

If we have all the raw elements in our long bones already, then why are we not shooting up in height? If we look at the system not in terms of elements, but in terms of the type of tissue that surrounds the system, then it is obvious. The deer antler has the mesenchyme progenitor cells aligned directly next to the skin tissue. The dermis and epidermis is far, FAR easier to stretch and push apart than bone. The mesenchyme directly creates the cartilage. I would suggest at this point then that the limiting element in how long the deer antler can grow to is the amount of mesenchyme that is still left in the antler tip. If that is the case, to restart the longitudinal growing process in the antlers of deer, we just have to inject a packet of undifferentiated pluripotent stem cells in the tip of the antler and it would restart the growing again.

So what is the external or surrounding element that is really the limiting contraint? It is the bones themselves. The mesenchyme is not directly touching the perichondrium. There is a relatively thick part of cortical bone that envelops any mesenchyme in the epiphysis. The bone is disrupting the mesenchyme-perichondrium adjacent layering that we find in the deer antler. Of course, the skin was also touching the air, or air molecules. In the human synovial joint the knees, the covering of the perichondrium is the articular cartilage. However what is covering the mesenchyme? It is not the perichondrium like in the antlers. It is a very thick layer of cortical bone. That is what is keeping the top of the bone, the epiphysis from pushing the bone longer due to chondrocytes produced.  If the cortical bone, even if it is at the top of the long bone was gone, we would have mesenchyme subjacent to the perichondrium. Then the long bone would increase longitudinally.

This post and main point would then validate the idea I had proposed before in An Alternative Explanation On Why The LSJL May Actually Help People With Closed Growth Plate Increase Height And Grow Taller (Big Breakthrough!)and then would do a YouTube video explaining the idea for the Hammer and Chisel Method in the postThe Chisel And Hammer Supplement Technique Explained Through Video

So then what can we actually do? What should the reader be taking away from this post?

Then can the same idea be transferred to humans? If we look at the bones of humans, can we find something of a system in adult humans where mesenchyme or a group of pluripotent or multipotent undifferentiated is touching perichondrium?? Actually yes. Let’s remember back to the idea that the perichondrium is actually two layers. The inner layer is around 15-20 cells thick. Those cells can theoretically be differentiated into the chondrogenic lineage. the way the outer layer of the long bones in the lower limbs is arranged next to each other would be similar to the deer antler arrangement.

So for regenerated longitudinal growth in deer antlers we have skin/perichondrium/mesenchyme/cartilage/bone

For the human long bone layering, we have  articular cartilage/outer fibrous collagenous periosteum/cambium layer of the periosteum/ cortical bone, mesenchyme.

There is only one layer-layer arrangement are where both system have the exact perichondrium/mesenchyme arrangement we are looking for. As luck would have it, it is also not being completely surrounding on all sides by the cortical bone. If it was surrounded by cortical bone, it would NEVER work since the cortical bone is way to strong to pull apart by the undifferentiated progenitor stem cells when they do differentiate into the chondrocytes we want them to be in. However since that one layer of mesenchyme is only 15-20 cells thick, we would only be able to get a very limited amount of real height growth, maybe 4-5 cms which Tyler and St.it has stated that they have received.

Note: This idea we are talking about is what has been proposed as a reason why the LSJL method works, due to appositional growth of the subperiosteal layer.

Note: The perichondrium is different from the periosteum, but I am assuming that the two connective tissues are similar since one of them comes from the other.

If we have that area, then I propose then at least theoretically we will be able to regrow cartilage using the mesenchyme with the right factors like the PTHrP and PPR directing it, and don’t need some type of cartilage implant from an external source. This is assuming that it is not completely surrounded by hard cortical bone.

Why Does The Epiphyseal Cartilage Disappear But The Articular Cartilage Remain? (Breakthrough!)

Some that may be perplexing for any real height increase researcher is to wonder…

Why Does The Epiphyseal Cartilage Disappear And The Articular Cartilage Remain? Aren’t they getting the same amount of load?

This was a huge question I started to ask myself and I think the search to answer this critical question lead me to one of the biggest discoveries in quite a long time. I would be directed to a paper which I had previous cited before in the post “Theories On Delaying Puberty To Extend The Growth Period

It is entitled “What Makes the Permanent Articular Cartilage Permanent?” which is not a real scientific study or article but onyl an editorial. However the information inside this 2 and a half page editorial really does shed light on something that has been on my mind.

What makes the articular cartilage special?

Analysis & Interpretation:

This will be my first attempt at trying to summarize my readings without trying to copy an entire abstract or the article. At this point I think that most readers don’t really care about the technical details. They are looking for the answer to their height increase solutions but are hoping that height increase researchers like me will do the hard scientific theory and research for them. And that is cool. I like learning about this stuff.

So for this post, when I am talking about the articular cartilage, I am talking about say the stuff that an orthopaedic surgeon would find at the distal end of the femur  when they open up the knee area and see what is there. I am really just going to look at the articular cartilage for one very special area in the body, in the knees, for the distal femur end the proximal tibia end, which are the two epiphysis ends that come together to make the synovial knee joint.

What I learn is that the articular cartilage, like all cartilage is a type of connective tissue. The tissue is not jammed with small cells in some organized fashion like some cells. There is the extracellular matrix of the articular cartilage and the chondrocytes inside. The matrix is rather hard in material strength. It covers the bones so that the bones themselves don’t touch, cause friction, and cause that local area in the body to become inflammed. The chondrocytes inside are kept safe by the matrix. They don’t so through hypertrophy (aka expand in volumetric size) like the chondrocytes you find in the epiphyseal cartilage and the chondrocytes are not enveloped by blood vessels since the cartilage seems to be able to protect itself from vascularization. Let’s remember from many of our previous research that vascularization for the epiphyseal cartilage is a bad thing for our desire to continue to grow longitudinally.

The articular cartilage manages to keep the cartilage phenotype around, preventing the intrusion of blood vessels from getting in. How is this done? The complete mechanism is not really known but in the last few years new evidence has been coming out to make a suggestion on what could be the cause. The writer notes that it seems that the usual suspects for growth factors like the TGF-Beta, BMPs, and the FGFs are produced in by the chondrocytes in the articular cartilage but not in the high level of amount that would be expected to say keep the cartilage and the chondrocytes alive. The real element that seems to keep the cartilage around, which a researcher named Klinger discovered was the angiogenesis inhibitor Chondromodulin Type-1. The matrix protein Chondromodulin Type-1 when used in lab pigs for testing showed that if Chondromodulin Type-1 is over expressed then cartilage will not get vascularized or ossified as quickly than cartilage which has little Chondromodulin Type 1. The results were shocking. The cartilage resisted calcification and vascularization for 6 months.

The administering of Chondromodulin was done two ways on cartilage defects…

1. either through the gene therapy method, which was to put the Chondromulin Type 1 complementary DNA into a vector and put the vector into cells which are pregenitors before they either differentiate into either chondrocytes or osteocytes. The chondorcytes then would overexpress on the chondromodulin protein in their production. The chondrocytes are then implanted in the defect area.

2. Or the vector without the cells is directly put in the defect.

From an in vitro context it seems that the Chondromodulin Type 1 has shown no effect in terms of overexpression of VEGF from looking at mRNA levels, but Klinger and the other researchers do note that they are looking at the process of the effects of Chondromodulin in a rather simplified system and that the effects of Chondromodulin in vivo can be more complex. They would also suggest that the matrix protein is something else that can prevent chondrocyte hypertrophy from blocking the expression of Collagen Type X, which is the type of collagen hypertrophic chondrocytes releases and is detected from histological testing.

The researchers would also ask whether Chondromodulin Type 1 is what can cause the down-regulation or inhibit the expression of  runt-related transcription factor 2 aka RUNX-2. The reason for this idea to check the effects on RUNX-2 is that RUNX-2 is one of the compounds that seems to regulate the production and/or expression of Collagen Type X and also VEGF type A

The researchers note that SOX9 should also be investigated. The SOX9 gene has been shown to be involved in the beginning stages of cartilage development. It seems that SOX9 is downregulated in the chondrocytes that are in hypertrophy in the growth plate during ossification. The authors of the study notes that another group  of researchers managed to show that SOX9 is very important in preventing the vascularization and endochondral ossification when just the hypertrophic chondrocytes were examined. The researchers state…

“Furthermore, they showed by in situ hybridization and real-time polymerase chain reaction that Vegfa, Mmp13, and osteopontin were all down-regulated in hypertrophic chondrocytes that misexpress Sox9, thus indicating that terminal differentiation was inhibited. Vegfa was also shown to be negatively regulated by direct binding of Sox9 to the Vegfa promoter”

It seems that the key original gene is the SOX9 gene which regulates the Chondromodulin Type 1. From looking at young chickens it is noted that both the SOX9 protein made by the Sox9 gene and Chondromodulin Type 1 are usually found in the same region in the body where there is no vascularization, ossification, and the cartilage stays around. From looking at studies with hearts, the same thing is found where the Sox9 expression seems to prevent heart tissue from becoming calcified. The exact heart part are the valves, which turn out not be heart tissue, but more cartilagenous in nature. The valves don’t seem to get vascularized which might turn them too rigid or hard to be flexible enough to deal with the rigorous demands of constant use in the human body.

Note what the researchers state below…

“Hence, chondromodulin 1 is most likely indirectly up-regulated by hypoxia, i.e., via SOX9, which is up-regulated under hypoxic conditions by hypoxia-inducible factor 2. Whether SOX9 directly binds and regulates chondromodulin 1 is an important unresolved question. However, this pathway provides one plausible mechanism by which this avascular tissue maintains its function throughout life, i.e., the chronic hypoxia in the cartilage helps maintain SOX9 expression levels that prevent vascular invasion (through, e.g., chondromodulin 1 induction) in addition to direct inhibition of terminal differentiation and subsequent calcification of the tissue as occurs, for example, in the murine growth plate when Sox9 levels greatly decrease prior to hypertrophy”

So it seems that this pathway guessed by this writer is

no blood vessels —> blood and O2 molecule never reaches the cartilage –> SOX9 is up-regulated –> Chondromoduline Type 1 is upregulated –> The Chondromodulin and Sox9 protein both prevents any vascularization/blood vessels from ever reaching into the articular cartilage, calcifying and ossifying it –> this continues through life as a positive feedback loop keeping the cartilage avascular.

We find that PTHrP (Parathyroid Hormone related Protein) seems to increase when chondrocytes in some medium when subjected to mechanical loading. The main thing to remember is that in articular cartilage, the chondorcytes inside are prevented from ever going through the differentiation process of hypertrophy and also prevent the process of vascularization

Implications For Height Increase:

This has shown finally what is the exact main difference between the epiphyseal cartilage and the articular cartilage. There seems to be a  greater amount of over expression of Chondromodulin Type 1 and Sox9 gene expression in the chondrocytes of the articular cartilage than the epiphyseal cartilage. Yes they are both hyaline cartilage but there is some difference in them. The Sox9 seems to either directly or indirectly regulate the Chondromodulin Type I production and they prevent the cartilage from becoming vascularized. Vascularized is the process of getting filled with blood vessels. Vascularization is what seems to lead to calcification and calcification is basically the process that kills off cartilages. They also might seem to prevent hypertrophy. We know that hypertrophy is needed for actual long bone endochondral ossification lengthening since the rate of bone longitudinal increase is positively correlated to the amount of hypertrophy the chondrocytes in the hypertrophic zone can go through (aka the bigger the better). We still need hypertrophy and some vascularization and then calcification of empty pockets to actually make us grow taller when we are still in the natural growing process. However we will need to realize that there will come a point in a person’s development where it will be needed to stop further vascularization and calcification to extend the amount of time for growth by keeping the epiphyseal plate cartilage still around, allowing for another method or technique to come in to add more mesenchyme or chondroprogenitor cells back into the reserve zone so that we can continue the bone lengthening more than it was naturally designed to go through.

How Badly Do You Want It? What Are You Willing To Give Up And Sacrifice For A Chance To Reach Your Height Goals?

sacrifice- chessSo many times I get messages where people ask me what they can do to grow taller. Some people who are very determined give very strong messages saying that they are willing to do anything or take any type of supplement to get the type of height that they want but I sometimes wonder whether they really want it as much as they claim.

The truth is that there is often a hidden unspoken exception to their height goals. This is the fact that they won’t go to the option or choose going through with the surgical method for height increase. They are willing to try any type of method or technique EXCEPT for limb lengthening surgery. Well in my opinion I think that they are then just not really truly serious about the endeavor then.

I know people who have been spending over a year (or two or three) taking the supplements, buying strange insoles, and clamping their legs using the Lateral Synovial Joint Loading method to get even 1 cm of real permanent height but they still don’t achieve any real noticeable height increase which can be more than just measurement error. They have probably spent over 1000 hours towards stretching, exercising, swimming, and such to hope for that permanent height gain as well as many thousands of dollars on trying every option under the sun except for the limb lengthening surgery.

But they always stop before going to the last, real, most obvious option. Surgery. So my question to the reader who seems to only kinda of want it “How badly do you want it? What are you willing to give up and sacrifice for a chance to reach your height goals?”

You say you can take the pain, and you are willing to put in the time, effort and make the multi-year commitment but why not choose the sure thing, the easy option.

I may be using a bad analogy but… to choose all the possible ways to increase height except limb lengthening surgery can be similar to what a sexually frustrated 30 year old virgins may try to do in learning how to pick up women, signing on to dating websites, and hiring matchmaking services but draw the line at just hiring a escort or prostitute for the sole purpose of just sex.

There is a clear solution for your height increase problems. Yes, it will be very expensive, maybe in the range of around 50,000-100,000 even. You will have to give up 1 year of your life, have to live in a different country in a hospital where you can’t speak the local language. You will go through excruciating pain when you turn that screw on the rod to pull your tibia or femur apart. You will have to go through at least 3-6 month of physical therapy just to walk again. But those are the things you have to give up for this one endeavor.

Just go to the forum MakeMeTaller.org and see how the people there treat the fact that limb lengthening surgery is just another normal aspect to their lives. A sizable portion of them went through with the surgery, sometimes even for just 4 cm of extra height, which can possibly be achieved through normal exercising and stretching, but what they show in terms of what outsiders may think is insanity or craziness in their dedication towards increasing their height, I look at them and it shows just how strong the human spirit is and how the strongest determination will give them what they wanted.

Since the dawn of humanity, the shorter half of human kind have had billions of people wishing that they were taller. However that desire and wish to be taller was something they kept secret, something they hoped would just happen to them, like a painless easy growth spurt that is natural and proportional. well maybe life will never give them that type of easy way for height.

When I look at many of the females who walk by me as I walk down the street in Gangnam, Seoul, South Korea which is the plastic surgery capital of the world, I feel both confused at the girls but also some admiration for the people who are willing to go under the knife and have surgeons cut open their face and cut off bone just so they can become more “beautiful”. These people felt that beauty is important so they are willing to do ANYTHING that they can to achieve that dream. Surgery is a accept way to enhance oneself in the region of the world I live in. In america, many people might try to look down at these people and say that these women who get plastic surgery are stupid, or insecure, or have low self-esteem, and maybe they are right, but that still does not take away from the fact that millions of young teenage korean females are willing to have the bones in their face broken, cracked, removed, etc. for something that they really want. Theire desire is strong.

And for our desires, our desire for height should be strong as well. If you only kind of want to be taller but not be willing to put in the work in terms of say gritting your teeth and go under the knife, then maybe you really just don’t want it bad enough.  There is pain, but one of the regular posters said that the pain they would feel in say 1 year of limb lengthening surgery to gain 10 cm or 4 inches of height increase will more than make up for the fact that they will gain the confidence to finally not be insecure or so fixated on their height anymore. For men, maybe their dating lives will improve and where once women rejected them on their height, the same type of women will finally give them a chance. These men have their own lives and felt that being taller is quite possibly the most important thing in their lives, more than say earning more money, getting a better car , or working out for those 6 pack abs. They chose to focus on this one aspect and go through with the surgery to get what they wanted.

Before Ilizarov came along and perfected the external fixator device which now bears his name and given him world recognition, there was absolutely NO CHOICES. Now that is a statue of Ilizarov in a part of Russia where there is also an orthopaedic clinic named after him. Now we are lucky to be in such a modern world and do finally have the option to be taller even after our growth plates close. We can get surgery. And from the research I have done the surgery can be not as resource intensive as one might expect. There are cases where a person can get 3 inches of height for $30,000 and will take around 6 months to recover in. The member Apoptoesis from the Make Me Taller forum would get the limb lengthening surgery twice, once from 5′ 6″ to 5′ 9″, and then again to go from 5′ 9″ to 6′ 2″. This shows that there is something we can do now.

The problem is just that maybe we just don’t want that growth or height increase as badly as we think we want it. The next time we say on a internet board or talk to ourselves telling ourselves that we should continue to do the stretching exercises and taking the supplements, maybe we are not being honest in ourselves on how much we are really willing to try and go through for our goals.

If I or any of the other height increase seekers really wanted it, I’d go for the limb lengthening surgery. I personally know a few friends who now work as Investment Bankers or Hedge Fund Managers or surgeons who pull in 7 figures a year so it is clearly not a money issue. Are these people who make so much money not willing to accept the idea of putting a small bit of money down and put their life on haitus for one year to get the guaranteed growth that they are looking for. Sure, some people would try to give the counter-arguement that the limb lengthening surgery is very dangerous with possibly serious cripplying consequences, but that is just another reason, even if it is a completely valid reason, for why they have let their own fears to create rationalization and justifications on why they are not willing to take the final, the easiest way for true permanent height increase that we have right now.

Our short grandparents or great grandparents never had this choice but we do have it. So are we willing or have enough of the desire to take this choice and opportunity or are we just going to sit and wait, and wish that some benevolent group of super genius researchers from some secret lab in the world will come up with a solution for our non-invasive height increase desires? Maybe that secret desire will never come to be.

Maybe it is time to accept the idea that we either choose limb lengthening surgery or accept our short height and move on with our lives. I can’t promise you as the readers that even after 10 years of dedicated, intensive research that I or Tyler would find the solution. Maybe we will never find it and give up, like Sky and Hakker before us.

Is it okay that you don’t get the growth and height increase you want or is your desire so strong that you would make the greatest sacrifice for this dream? 

A Honest Guide On How To Possibly Increase Height And Grow Taller, For The Person With Closed Epiphyseal Growth Plates

Not available at this time – Earliest release date: June 1, 2014

A Honest Guide On How To Possibly Increase Height And Grow Taller, For The Person With Closed Epiphyseal Growth Plates

An guide on Honest, non-BS, logical, scientifically validated ideas to possibly increase the growth rate of height increase during the years when the growth plates are completely closed.

Price Of This Product: Not sure yet

  • Length Of Product: over 200 pages. – this will be similar in volume like a thesis application for Doctoral degree
  • Number Of Actual Proposed Ideas, Methods, and Techniques You Can Implement: unknown at this time.

The “book” will be quite expensive. There is no doubt about it. If you want one of the regular E-Books that some Internet Marketer who uses Clickbank to go to the – Free Stuff – or The Library section. Those E-Books and E-Products have the regular type of information which you would find in most books. This


Note #1: Unlike the other product which is for open growth plate, there is indeed a Refund for this product. A 30 days FULL refund for this product.

The reason why this product has a refund and the other product doesn’t is because of two main reasons.

  1. The price for this product is going to be very high. Many who do want this may not be able psychologically part with this type of cash, if not most people would not be willing to give up that time of time for such an endeavor.
  2. The fact is that this whole venture to try to find a real non-limb lengthening surgerical way to increase height is INSANELY DIFFICULT. There are multiple channels and avenues of research I have tried to look into and most of them seem to have little real chance of working. This is little guarantee that the methods I will put in the book will even be able to give 1 cm of height increase.

The refund policy is my way of giving the buyer a way to get out of lossing $300 if they realize they can’t do the steps in the method since there is a high probability and chance of failure and the idea not working.


The Truth: All the information you will find in the book, you can find at some point on the website. At some point I have talked about one of the main ideas already. What I have done is take all the most useful and applicable content from the last 1000 posts and placed them in one place.

At some point I realized that the Supplement Guide and the Exercise Program Guide was not enough. The section I put up for FAQs to help slow down the onset of dozens of emails I get each day still did not stop the emails. This is the way I can put a full stop to the emails. This “book” is the best advice that I can give at this stage in my research.

I will NEVER lie or try to deceive the readers and the visitors to this website/blog. Everything I am showing you is the best content and “secrets” that I have found. There is NO Magic Pill.

Warning: Do not purchase this product on the spur of the moment. I will just say it right now. Do not purchase this product on the spur of the moment. Before you buy this product, ask yourself…

How badly do I really want it? How much do I really want to increase my height? What am I willing to give up and sacrifice to gain the amount of height increase that I am hoping for?

I wrote in a post about this exact issue because I understand the psychological resistance there is with this type of purchase. You have been tricked before. The scam artists are many and this entire niche is a cesspool of scams and frauds. I have looked at the past work of the other height increase researchers and seekers before me. I have read everything I could about the research Sky (from EasyHeight.com and LimbCenter.org), Tyler (from HeightQuest.com), Hakker (from GrowTallForum.com), the GrowTallerForum.com (the other small less popular forum), the GrowTallInfo.com forum, Alkoclar, XCrunner211, Bababooey, GiantScientific.com, the people on the MakeMakeTaller.org forum, and any other resources I have been able to find on the internet.

If you are going to put your (or your parents’, siblings’, friends’) credit card information in, I hope you are really ready to make the type of commitment to say that you are really goig to buy the neccesary equipment, make a true commitment, and section off a portion in the day for time to implement the idea out.


Final Message For Right Now 1/26/2013:

If you have managed to read this far down to the post/message, I’ll say truthfully that this book/E-Product has not been written. It will be the 1st edition. Over the next 3-5 years, I will be editing and revising this book to be more up-to-date with any new breakthroughs, ideas, and news I hear. It will also have less spelling and grammatical mistakes.

There is a very good reason for this. It is because I haven’t found any methods or results which really do seem to have a high chance of working for the person who has closed growth plates.

I have decided that even if I get over my own height insecurities and my own issues on how tall I am, I will not stop in my research. This is my calling. I am here to help the world and hopefully make a real difference and make other people’s lives a little better.

So please put your full name and personal email information below to make a reservation for the option to buy the book when it finally is finished. I promise that when the book is finally finished, I will give you a email notice/message that the book is ready for you to easily buy and download for use. There is also a very good chance that I will upload the book to Amazon.com as a Kindle E-Reader file.

A Honest Guide On How To Possibly Increase Height And Grow Taller, For The Person With Open Epiphyseal Growth Plates

Not available at this time – Earliest release date: July 1, 2013

A Honest Guide On How To Possibly Increase Height And Grow Taller, For People With OPEN Epiphyseal Growth Plates

A guide on Honest, non-BS, logical, scientifically validated ideas to possibly increase the growth rate of height increase during the years when the growth plates are still open.

Warning #1: Do not purchase this product on the spur of the moment. I will just say it right now. There is NO REFUND. Please read that last part again.

Price Of This Product: Not Sure Yet

  • Length Of Product: over 100 pages for sure. – at this point it is still being developed and in the infancy stages of being finished (ie. 4-5 pages finished)
  • Number Of Actual Proposed Ideas, Methods, and Techniques You Can Implement: over 10 techniques, ideas and things which have been documented by real researchers and medical professionals have proven through experimentation in the laboratory to work.

First thing first, the most obvious thing about the book – This book is going to be quite expensive

There is no doubt about it. If you want one of the regular E-Books that some Internet Marketer who uses Clickbank to sell a weak content based book, go to the – Free Stuff – or The Library section. Those E-Books and E-Products have the regular type of information which you would find in most books. This book is real and detailed of only technical information. However that technical information is only used to validate and show definite proof from sources, citations, and references that scientific professionals in the past have seen the same type of results and phenomena.

In this book I will be giving specific step by step directions on what to do. The book is a guide and an instruction manual. Sure, I can spend the next 40 minutes giving as many fluffy reasons on why you should buy this book to justify the of price but I can’t. I am going to let the content and the information built its own reputation.

The Truth: All the information you will find in the book, you can find at some point on the website. At some point I have talked about one of the 4 main ideas already. What I have done is take all the most useful and applicable content from the last 1000 posts and placed them in one place.

At some point I realized that the Supplement Guide and the Exercise Program Guide was not enough. The section I put up for FAQS to help slow down the onset of dozens of emails I get each day still did not stop the emails. This is the way I can put a full stop to the emails. This “book” is the best advice that I can give at this stage in my research.

I will NEVER lie or try to deceive the readers and the visitors to this website/blog. Everything I am showing you is the best content and “secrets” that I have found. There is NO Magic Pill.

Warning #2: Do not purchase this product on the spur of the moment. I will just say it right now. There is NO REFUND. Please read this again. Think rationally about this choice and ask yourself whether you are really going to put the energy, effort, and time to implement the suggestions and steps given.

The reason There is no refund is because I am around 80-85% confident that the methods described in the book will work in increasing the rate of longitudinal growth in the long bones of the person who is still developing with OPEN growth plates. I don’t have 100% confidence because that would be arrogant of me to think I would know all the answers.

The whole endeavor of trying to increase one’s height is a very tricky and sensitive subject.

The most important question you probably should ask yourself is….

How badly do I really want it? How much do I really want to increase my height? What am I willing to give up and sacrifice to gain the amount of height increase that I am hoping for?

I wrote in a post about this exact issue because I understand the psychological resistance there is with this type of purchase. You have been tricked before. The scam artists are many and this ENTIRE niche is a cesspool of scams and frauds. I have looked at the past work of the other height increase researchers and seekers before me. I have read everything I could about the research Sky (from EasyHeight.com and LimbCenter.org), Tyler (from HeightQuest.com), Hakker (from GrowTallForum.com), the GrowTallerForum.com (which is not related to the more popular forum), the GrowTallerInfo.com forum, Alkoclar, XCrunner211, Bababooey, GiantScientific.com, the people on the MakeMakeTaller.org forum, and whatever else I have been able to find.

If you are going to put your (or your parents’, siblings’, friends’) credit card information in, I hope you are really ready to make the type of commitment to say that you are willing to actually go through with the stuff that the book talks about.

I don’t intend for this book to make a lot of money. I know very few people would accept the idea of paying $100 for a book. and that is perfectly okay. If I sell not one copy in its existence I will still be okay. This is a book which I am writing for my future children, which I will use on my own children in time since I have confidence in the ideas I propose. This book is my legacy.

I don’t intend to take down this website for a long time, at least until the internet changes so much that this type of format can no longer function. Sky from EasyHeight.com and LimbCenter.org had those sites up for over 6 years. Hakker had his website up for around 4-5 years. If you would like to see what was on those websites you can use the Wayback Machine that archives old, dead websites from the entire internet.

This website/blog is not going away, since I know for a fact that I am making a difference in this world by doing more research on this subject.

[Disclaimer: As always I am not a medical professional but just an obsessive amateur researcher on auxology and height increase, so taking any type of advice from me is at your own risk. I can not and will not be held responsible legally or financially for any injuries or adverse affects that might happen to the individual who does indeed choose to go through the procedures I talk about. I have a high level of  confidence in my own product and my research can indeed stand up to close scrutiny, scientific scepticism, and criticism by people from the medical establishment.]

Before you click on that link below to buy this book, read this final message very clearly!

This book is for people with OPEN EPIPHYSEAL GROWTH PLATES. If you are still at the age or stage in your life where natural normal growth is still possible since your growth plates are around, then this book is okay to buy. –

– If however your epiphyseal growth plates aka physis is CLOSED, gone, ossified, etc. whatever you want to call it, then do not buy this book. It will NOT help you. Buy the CLOSED EPIPHYSEAL PLATE BOOK instead, assuming that I ever do manage to finish that book and find real viable ideas and techniques.  –

So please put your full name and personal email information below to make a reservation for the option to buy the book when it finally is finished. I promise that when the book is finally finished, I will give you a email notice/message that the book is ready for you to easily buy and download for use. There is also a very good chance that I will upload the book to Amazon.com as a Kindle E-Reader file.

What Are The Chances For Me To Go Through A Late Teenage Years Or Late Life Growth Spurt?

One of the more common questions posed by people who email to the website email is them asking the question which is a variation or derivative of “What Are The Chances For Me To Go Through A Late Teenage Years Or Late Life Growth Spurt?

This is a really common question that I see on all of the height increase and grow taller boards. For these people they are only in the very early stages of learning about this endeavors.

I have thought about putting this question in the FAQ section of the website.

If felt that the entire question can be almost completely answered by reading the two posts below

Hi, I’m ENTER YOUR AGE years old. Am I Still Growing? Can I Still Grow Taller?

What Is The Most Height Gain One Can Achieve Through Exercises And Stretching After Puberty And Growth Plate Closure?

While the question posted for this post implies that the person asking the question is hoping that a miracle will happen to them which will let them do nothing but be passive in their achievement of height increase, the question and post I linked above implies that the person who wishes to be taller is willing to do more than just hope and may be more active and assertive in their approach for height increase.

To answer the question more directly is is worth pointing out the medically defined age range for most males and females for when they stop the natural growth process.

For males, they stop growing around the 17-19 age range – This is basically exactly the end of the teenage ages since the technical definition of the end of being a teenager is around 18 years old.

For females, the stop growing around the 15-17 age range – This is basically a little below the end of the teenage years. However we do note that females in general even in their development years mature faster than males, in terms of bone maturity and also emotional and mental maturity too.

If the person asking is hoping for a late teenage years growth spurt, then they would have to be more exact on how old they are exactly. There is a major different between 17.6 years old and 18 years old for men. There are enough cases seen where the male manages to continue to add 1-2 extra inches after even the 18 years point. This is due to maybe from the late closure of the male growth plates and also the longer, bigger tail of the bell curve of the distribution of height tabulated for men. The standard deviation magnitude for the male population is large than the standard deviation magnitude for the height bell curve distribution of females.

In all honestly, I would tell the individual that their chances are very low, maybe around 0.1-0.5% if they are anywhere past the age of 17 for a female and 19 for a male. There are many people who might try to counter-argue this assessment by telling me and recounting a story of how their relative, themselves, or one of their friends beat the age range and was the exception but the numbers don’t lie.

Most people who do contact this website are already in their 20s so their odds are severely reduced. I am talking about it to mean that in terms of percentages they might have a 0.001% chance that they would even be able to get 1 inch. However this does not mean that they can’t get some real height increase by focusing on stretching out their vertebrate and realigning their posture. A large percentage of people in a given population has the potential to gain upwards (or sometimes slightly more) of 1 inch in height increase through stretching and posture correction int their 20s. However what they are doing is more like body remodeling or modification, which is NOT a growth spurt.

Growth Spurts imply that the bones in their body went through further the process of endochondral ossification and the height they did achieve is permanent, which is something that won’t go away if they stop doing the stretching.

Maybe the person who messages me might think that they are somehow special, unique, or have a situation which means that they are excluded from the majority but fit that very, very small minority of people who can still grow, but that is always assuming that they think that their growth plates are still open. I would not want to wager that the person has their growth plates still around, but are gone. If a person doesn’t have their growth plates anymore in their limbs, they still have some cartilage in their vertebrate which might still be around which will contribute to the person’s overall height through appositional growth but if those vertebrate growth plates disappear, then growth spurts are almost impossible.

There is one unique case where it is suggested that growth spurts might still be able to occur that was with with the now passed Tanya Angus. Her biography showed that she apparently stopped increasing in height when she was in her teens but her growth was reactivated when she was around 18, which is the age when most females would have complete closure of their cartilage. Of course Angus had the most severe case of Acromegaly that has ever been documented. Where most pituitary gland tumours which cause human gigantism are benign in nature, Tanya Angus had one which seemed to more malignant, at least in terms of the fact that her tumour seemed to grow bigger. If we can prove that Angu’s plates were in deed gone before her pituitary gland was activated, this might prove the idea that even with all the growth plate closed, growth spurts still might be able to happen where the body is enlarged in every single way, not just in terms of height.

So at this point, hope for the best but expect the worst. Be prepared to accept the idea that maybe you are not going to get any growth spurt but be grateful if it does happen. Sometimes the growing does happen, like what happened with Dennis Rodman with his crazy 10 inch of growth at the age of 20, but those cases are very, very rare.