At this point it may be smart to look over all the data and information we have collected and studied and access where we are in the research. I am planning on looking over some ideas and methods which I had gone over in the very beginning, around autumn of last year to maybe rewrite some old posts since the level of my understanding of auxology and bone physiology has increased since then.

I wanted to go over the idea of using Bone Morphogenetic Proteins to possibly increase height and make people taller again. The first time this idea towards connecting BMPs with the endeavor of Height Increase I had let someone named Kazlina or Nicki write it. The post is “Increase Height And Grow Taller Using Bone Morphogenetic Proteins, BMPs (Guest Post)“. At the time I only understood maybe 60-70% of the material of what she wrote but now I can really look over the original article to see if there is more to add on this subject.

Note: As for Nicki Or Kazlina, who seemed to be a big member in the online height increase community just a few years ago, I don’t have any contact with her anymore. After trying repeatedly to get her on the phone for a Skype interview for a Podcast, she has stopped responding back to my messages. I guess the research collaboration with her is gone, at least for right now. Best of luck to her in whatever she wishes to pursue. 

I am almost certain that at some point we will need to look over the ideas I had posed previously and go over past articles to see if we missed anything the first time around. I know that during the early months of this website I had written and posted so much that it was nearly impossible for me to have gone in detail and develop a real deep understanding of growth mechanics and mechanisms from only skimming those articles back then.

The bone morphogenetic proteins has been consistently shown to have amazing osteogenic and chondrogenic potential. I have seen that BMP-7, aka OP-1 can have very good healing properties towards intervertebral disks in the post “Osteogenic Protein 1 OP-1 Or Bone Morphogenetic Protein 7 BMP-7 Can Increase Intervertebral Disk Height (Important)”

At least for BMP-7 or OP-1 they have the ability to increase collagen and proteoglycan content in the annulus fibrosis of so it is very likely possible that the torso can be increased by at least a few millimeters from injections of BMP-7 close to the disks.

What I would propose towards limb or leg lengthening to get get taller is that we need to focus on creating cartilage and cartilagenous tissue. BMPs are great at healing bones with adding them with scaffolds, cell seeds, and other growth factors, but in the research I (and the other researchers) have managed to find at least a dozen ways to get bones to heal fasters through various techniques on bone growth and bone healing.

BMPs are a type of growth factor that is part of the TGF-Beta superfamily. We need to find BMPs that are better at chondrogenesis when they are added in vivo than osteogenesis. I am proposing that it is possible that the lineage an injected BMP will take may be partly due to the tissue and environment  it is placed in.

This means that I would rather combine BMPs with a seed colony of cartilage to get things to start growing. So which BMP’s are currently shown to have high chondrocyte differentiation potential?

So far, the best studied BMPs are the BMP-2 and the BMP-7. Others are less well known and less studied.

Study #1: From the study “Osteogenesis versus chondrogenesis by BMP-2 and BMP-7 in adipose stem cells.” it would seem that from at least the progenitor cells which we find in adult human bone marrow, which are known as the adipose tissue derived mesenchymal stem cells (AT-MSCs) the BMP-7 is the one that will go into the chondrogenic lineage while the BMP-2 is the one that will give us bone tissue.

So to outline…

• The closest progenitor cells we have next to the long bones is the adipose tissue derived mesenchymal stem cells found in the marrow which is encapsulated by the inter-medullary cavity of each long bone in the adult human body. 
• The shortened named for adipose tissue derived mesenchymcal stem cells is AT-MSCs.
• We will turn AT-MSCs into bone tissue using BMP-2
• We will turn AT-MSCs into cartilage tissue using BMP-7

Study #2: From the study “Differential effects of BMP-2 and TGF-beta1 on chondrogenic differentiation of adipose derived stem cells” it would seem that we can get the BMP-2 which would create bone tissue alone to create cartilage tissue if it is combined with TGF-Beta1. The alkaline phosphatase creation by BMP-2 alone is inhibited, while glycosaminoglycan is also increased. Collagen Type X and Collagen Type 2 mRNA are both increased. 

So to outline…

• The term adipose-derived adult stem cells is shortened to ASCs. This is the same as AT-MSCs.
• BMP-2 and TGF-beta1 together causes ASCs to develop into chondrocytes completely.
• increased Glycoaminoglycans, Collagen Type X, Collagen Type 2, while inhibiting Alkaline phosphatase.

Study #3: “Regulation of differentiation pathway of skeletal mesenchymal cells in cell lines by transforming growth factor-beta superfamily.“

Main Take-away: BMP-2 induces the undifferentiated mesenchymal progenitors to differentiate into osteoblasts, chondrocytes and adipocytes

Study #4: “[Recent advances in researches on bone formation–role of BMP in bone formation].”

Main Take-away: BMPs not only inhibit myogenic differentiation but also convert differentiation pathway of some myogenic cells into an osteoblast lineage

Study #5: “Adenovirus mediated BMP-13 gene transfer induces chondrogenic differentiation of murine mesenchymal progenitor cells.”

This study was interesting because it seems that while BMP-13 which is also known as CDMP-2 which is short for cartilage-derived morphogenic protein-2 seems to sort of support the differentiation of the progenitor cells towards chondrocytes but not to complete differentiation.

The important points to learn from this study are…

• BMP-13 is still expressed in human growing bodies in the articular cartilage
• BMP-13 aka CDMP-2 compound was found to be very good at healing tendons after surgery. 
• BMP-2 stimulated the overal endochondral ossification process.

I would like to note the important parts of what is said in the results…

“Analysis of gene expression in hBMP-13-transduced cells demonstrated presence of cartilage-specific markers, absence of hypertrophic chondrocyte specific markers, and upregulation of proteoglycan biosynthesis. In particular, hBMP-13-transduced cells had significantly less and delayed expression of alkaline phosphatase activity and calcium mineral accumulation than hBMP-2-transduced cells…In summary, hBMP-13, while stimulating chondrogenesis, failed to support differentiation to hypertrophic chondrocytes and endochondral ossification similar to hBMP-2. Thus, this may prove to be a useful strategy for cell-based regeneration of articular cartilage.”

• BMP-13 by itself, if not added into a genetically engineering adenovirus seems to push the progenitor cells towards the chondrogenic lineage while keeping the chondrocytes from ever going into the hypertrophy phase which means that they might have uses towards the regeneration of articular cartilage. 

Let me note at this point something that Tyler said as a comment on the post “How To Buy Your Own Bone Morphogenetic Proteins From Invitrogen And Life Technologies”

“Human Bone Marrow Mesenchymal Stem Cells already express BMP-2, 4, and 6 and spontaneously differentiate into osteocytes when placed in culture. So more than BMP-2 is needed for hBMSC chondrocyte differentiation.”

It seems that his research agrees with mine but the claim that the mesenchymes can already create BMP-2, 4, and 6 resulting in only osteocytes means that we have to look for some else besides only using the BMP-2, 4, or 6.

Study #6: Osteoinductive growth factors can aid bone growth in orthopedic procedures

“…But only some BMPs form ectopic bone….The most osteoinductive factors are BMP-2, -6 and -9. The intermediate ones are BMP-4 and -7 which have more limited inductivity properties with mesenchymal stem cells”

What this source seems to suggest is that the BMPs that have the most effect towards bone tissue growth are BMP-2, 6, and 9 which is something which past research seems to agree with. It seems that while the BMP-2 has less osteoinductive abilities, it is much better for making cartilage tissue…

The other thing that this source reveals is the two major companies who are willing to sell the two types of BMPs allowed by the FDA…

FDA Approved BMPS

1. Recombinant human BMP-2 – Used For: INFUSE Bone Graft – Company: Medtronic
2. BMP-7 aka OP-1 – Used For: Implant – Company: Stryker Biotech

Study #7: Comparative review of growth factors for induction of three-dimensional in vitro chondrogenesis in human mesenchymal stem cells isolated from bone marrow and adipose tissue

So it seems that bone marrow derived adult human stem cells and adipose derived stem cells can both differentiate into chondrocytes or cartilage cells. They are known as MSCs and ASCs

The study was great because they did a complete review and analysis of the various types of growth factors which would be really good in inducing chondrogenesis in vitro…

“To date, the most promising growth factors for chondrogenesis appear to be TGFbeta-3 and bone morphogenetic protein (BMP)-6”

What is sort of contradictory information from this study was that the people said that the best growth factors were…

• TGF-Beta3
• BMP-6

I can definitely believe TGF-Beta 3 but I am not sure about the BMP-6 since in the last source it said that BMP-6 was one of the best osteoinductive growth factors. How can BMP-6 be the best at making progenitor stem cells turn into bone tissue and cartilage tissue? It has to be better at turning new cells into one of the two types of tissues, not both.

For these people from 2010 in North Carolina State University (NCSU) they say this

• Best for MSCs – TGF-Beta3 & Dexamethasone (and possibly addition of BMP-6)
• Best for ASCs – All three growth factors together’

What is interesting is that the researchers do admit that the chondrogenic lineage that is formed don’t seem to be all that stable.

Study #8: Combination of transforming growth factor-beta2 and bone morphogenetic protein 7 enhances chondrogenesis from adipose tissue-derived mesenchymal stem cells.

This study was very short and sweet managing to comfirm previous studies…

Chondrogenesis will result from adipose tissue derived MSCs using: TGF-Beta2 & BMP-7

This study was most insightful since there was a 7 groups analyzed..

1. Group 1: Negative control Group w/o any growth factors but do have 5 ng/mL TGF-Beta2
2. Group 2: BMP-2 at 100 ng/mL
3. Group 3: BMP_6 at 100 ng/mL
4. Group 4: BMP-7 at 100 ng/mL
5. Group 5: TGF-Beta2 & BMP-2 (5 & 100 respectively)
6. Group 6: TGF-Beta2 & BMP-6 (5 & 100 respectively)
7. Group 7: TGF-Beta2 & BMP-7 (5 & 100 respectively)
8. There was also a positive control group where the MSCS were bone marrow derived and added with 5 ng/mL of TGF-Beta 2

This shows that when we compare the effectiveness in being able to create cartilage tissue of BMP2, 6, and 7, by themselves alone and with another growth factor being TGF-Beta2, the BMP-7 is the best when it is used in the BMP-TGF-Beta combination.

The results from this study are very interesting and agree with many older points, but don’t agree with the two points made in study 6 and study 7.

Conclusion

So it seems that some people are saying that the best growth factor combination is using BMP-6 with dexamethasone and others are saying the best is TGF-Beta2 & BMP-7. At this point, I would say that the single best chondrogenic growth factor that will lead to cartilage formation is probably the TGF-Beta2 & BMP-7 combination. For me, it would seem that the TGF-Beta, 2 or 3, is good combined with any growth factor. I have not done enough research, but I am going to assume right now that the chondrogenic synergistic effect of adding either TGF-Beta 2 or 3 with a BMP is about the same change for all types of BMPs (2, 6, 7, and 13).

So I am saying that the best option I know of right now, besides using the GDF-5 is the BMP-7 as the main growth factor to be added. With it, we will supplement its chondrocyte differentiating ability with TGF-Beta2. There is some evidence that maybe BMP-13 would help too, but that is still undetermined at this time.