Monthly Archives: August 2020

New LSJL paper and update on revising LSJL method

So I’m revising the LSJL method to explore what I was doing when my medical records show I grew.

Is it still LSJL if you’re using impact and not loading the synovial joint region?  I’m trying to use impact ball pein hammer as an alternative to clamping as clamping as always had slipping problems.  In Hiroki Yokota’s methods, they could use advanced devices to avoid slipping.

Here’s the study that shows the LSJL worked on adult mice.  Although the mice in that study did not have senescent growth plates as the control group adult group grew as well.  The difference between mice and humans is that when mice growth plates become senescent they don’t seem to fuse.  This may lead to better force transduction between the epiphysis and the diaphysis.

Thus, new LSJL may be tapping on the longitudinal ends of the diaphysis of the bone.  The diaphysis is the core of the bone.  The epiphysis of the bone is highly load bearing so force may dissipate before it ever reaches the diaphysis which contains a lot of core bone materials.  Distraction osteogenesis works by fracturing the diaphysis not the epiphysis.  By tapping the diaphysis you can feel the force transmit throughout the entire bone.

The issue is that there are people who already apply force to the diaphysis of the bone.  Muay thai kick boxers who kick their shin’s.  Rolling a bar over your shin is not the same as the force won’t be the transmitted deeply and throughout the entirety of the bone.    Kicking an object with your shins will be in the center of the shin and not near the end of the shin thus there would be as an effective pressure gradient throughout the entire bone.    Muay Thai fighters have also broken their shins this way which is a step for lengthening bone in distraction osteogenesis….But unless the break is in a controlled manner it won’t result in bone growth.

So the difference between this and muay thai is the site that the impact occurs(at the starting points of the diaphysis rather than the middle), that it occurs in a more controlled fashion(although there are probably some muay thai fighters that can kick very precisely), that the impact loading is smaller and more rapid(frequency is an important factor in stimulating bone growth), and that the bone is the object being hit rather than the object doing the hitting(this may affect how the force is transmitted throughout the bone).  In addition, a ball pein hammer as a smaller surface area which increases the pressure transmitted to the bone rather than a larger object

It’s easy enough to do this for the radius, ulna, and tibia as those bones are well exposed.  The humerus and femur are covered by muscle but I seem to have potential sites.  But I can always just grow from the tibia and forearm bones and then use that proof to develop methods.  So I’ll see if I can grow and then share the method…

I’d argue that it still uses the principles of LJSL as it involves loading one site of loading to stimulate growth throughout the entire bone.  It involves stimulating the same principles: interstitial fluid flow, hydrostatic pressure, and pressure gradients.

Here’s the LSJL study, unfortunately not on longitudinal bone growth but there are some growth plate pictures:

Mechanical stimulations can inhibit local and remote tumor progression by downregulating WISP1

“Mechanical stimulations can prevent bone loss, but their effects on the tumor‐invaded bone or solid tumors are elusive. Here, we evaluated the effect of knee loading, dynamic loads applied to the knee, on metastasized bone and mammary tumors. In a mouse model, tumor cells were inoculated to the mammary fat pad or the proximal tibia. Daily knee loading was then applied and metabolic changes were monitored mainly through urine. Urine samples were also collected from human subjects before and after step aerobics. The result showed that knee loading inhibited tumor progression in the loaded tibia. Notably, it also reduced remotely the growth of mammary tumors. In the urine, an altered level of cholesterol was observed with an increase in calcitriol, which is synthesized from a cholesterol derivative. In urinary proteins, knee loading in mice and step aerobics in humans markedly reduced WNT1‐inducible signaling pathway protein 1, WISP1, which leads to poor survival among patients with breast cancer. In the ex vivo breast cancer tissue assay, WISP1 promoted the growth of cancer fragments and upregulated tumor‐promoting genes, such as Runx2, MMP9, and Snail. Collectively, the present preclinical and human study demonstrated that mechanical stimulations, such as knee loading and step aerobics, altered urinary metabolism and downregulated WISP1. The study supports the benefit of mechanical stimulations for locally and remotely suppressing tumor progression. It also indicated the role of WISP1 downregulation as a potential mechanism of loading‐driven tumor suppression.”

You can see the growth plate in figure 1F.  The growth plate looks thicker as does the articular cartilage.  The tumor of course plays a confounding variable.  You can also see that the entire bone of the loaded group looks different….

“As a mouse model of skeletal loading with C57BL/6 female mice, we conducted knee loading that applied sinusoidal compressive loads to the knee (Figure S1A). Dynamic loads of 0.5, 1, and 2 N at 2 Hz induced loading magnitude-dependent strain. Loads of 0.5 N (peak-to-peak), which will be used hereafter, induced approximately 100 με (axial compression) and 50 με (lateral tension), with a phase shift of ~180° between these two strains”

So the paper shows more promise that joint loading or methods that use it’s principles can induce longitudinal bone growth.

Medical records show I did in fact gain height from LSJL(or related method)

You can see the consistency so we can safely rule out measurement error.  I was also well in my 20’s so natural growth can be ruled out.  Either there was microgrowth throughout all years or there was a method used between 2012 and 2014.  I didn’t realize such a thing recently because I’ve never gone through my records before.

If it was in a method that I used between 2012 and 2014 and not incremental growth then it was the chisel and hammer method that I was looking at the time.

Here’s the method explained.  So I’m going to try to do this method again.

 

Breakthrough-Indirubin looks like a very promising height increase compound

Indirubin has shown promise before as a CXXC5 inhibitor. ” elongated tibial length through delayed senescence and further activation of the growth plate in adolescent mice.”<-further activation of the growth plate is what is most interesting.

We have to be on the lookout for indirubin derivative, KY19382.

Here’s a patent PHARMACEUTICAL COMPOSITION CONTAINING INDIRUBIN DERIVATIVE AS ACTIVE INGREDIENT

Interesting parts of the patent:

“The composition of claim 7, wherein the compound promotes bone growth and/or increases bone thickness.

12. The composition of claim 7, wherein the compound promotes chondrocyte proliferation, induces differentiation of osteoblasts, and/or activates β-catenin stabilization and nuclear translocation of β-catenin.”

“The composition for promoting bone length growth in accordance with the present invention has the promoting effects on both proliferation of chondrocytes and differentiation of osteoblasts, thereby increasing both bone length and thickness (bone density). Therefore, because it has the advantages of a wide range of prescriptions for various age groups, it can be usefully used as a pharmaceutical composition that can promote the growth of bone length and thickness.”

“The food compositions of invention, if manufactured as a beverage, is essential at the rate indicated, and there is no specific restriction on the liquid composition, such as ordinary drinks, and may contain several flavoring agents or natural carbohydrates as an additional ingredient. Examples of natural carbohydrates described above are monosaccharides (e.g. glucose, fructose and the like), disaccharides (e.g. maltose, sucrose and the like), and polysaccharides (e.g. dextrin and cyclodextrin, as well as common sugars such as xylitol, sorbitol and erythritol). As flavoring agents other than those described above, natural flavoring agents (e.g. taumatine, stevia extracts, such as fume-based A and glycirrhizine, and synthetic flavoring agents, such as sakarin, aspartame) can be advantageously used. The ratio of the above natural carbohydrates is generally about 1 to 20 g per 100 ml of the composition of this invention and, preferably, about 5 to 12 g.”

So seems like it will be a beverage which could mean it’s for everyone!!!!!!!!!!

Here’s another interesting study:

Indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway

“we identified indirubin-3′-oxime (I3O) as a compound capable of enhancing longitudinal bone growth. I3O promoted chondrocyte proliferation and differentiation via activation of the Wnt/β-catenin pathway in vitro. Intraperitoneal injection of I3O in adolescent mice increased growth plate height along with incremental chondrocyte maturation. I3O promoted tibial growth without significant adverse effects on bone thickness and articular cartilage. Therefore, I3O could be a potential therapeutic agent for increasing height in children with growth retardation.”

Fig. 2Fig. 2

Look at the tibia growth in fig2 at 5uM it is sick!  Although a bit curved.  If you look at 2a it looks fairly normal though.

“I3O significantly increased the mRNA levels of early chondrogenesis markers, such as Col2a1 and Sox9. In addition, I3O treatment increased the mRNA levels of fully differentiated hypertrophic chondrocyte markers, such as Col10a1, Vegfa, Alp, and Mmp13, as well as prehypertrophic chondrocyte markers, such as Runx2 and Mmp9. Transcriptional induction of these genes by I3O treatment was suppressed by knockdown of Ctnnb1″

“The practical usage of I3O is advantageous because it is an indirubin derivative that is the main active ingredient in a traditional Chinese medicine, Danggui Longhui Wan”<-even if indirubin is in the Danggui Longhui Wan we still don’t know if it’s effective.

All height seekers should be monitoring Indirubin

Here’s a biohacker thread on indirubin.  One interesting comment: “The issue seems to be that the drug has not been studied in humans, nor in vivo for this application. With the current understanding of hormono-dynamics, GH secretagogues + antidiabetic compounds (metformin) seem to be the best bet to enhance height safely in adolescents.”  On metformin “Metformin in this case would mediate any deleterious effects on glucose metabolism exerted by the gh secretagogues which are known to mess up glucose tolerance.”

Here’s some studies with updates on Indirubin:

ERα/β/DMP1 axis promotes trans-differentiation of chondrocytes to bone cells through GSK-3β/β-catenin pathway

 “Estrogen-induced premature closing of the growth plate in the long bones is a major cause of short stature after premature puberty. Recent studies have found that chondrocytes can directly trans-differentiate into osteoblasts in the process of endochondral bone formation, which indicates that cartilage formation and osteogenesis may be a continuous biological process. However, whether estrogen promotes the direct trans-differentiation of chondrocytes into osteoblasts remains largely unknown. Chondrocytes were treated with different concentrations of 17β-estradiol, and Alizarin Red staining and alkaline phosphatase activity assay were used to detected osteogenesis. Specific short hairpin RNA and tamoxifen were used to block the estrogen receptor (ER) pathway and osteogenic marker genes and downstream gene expression were detected using real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining. The findings showed that 17β-estradiol promoted the chondrocyte osteogenesis in vitro, even at high concentrations. In addition, blocking of the ERα/β pathway inhibited the trans-differentiation of chondrocytes into osteogenic cells. Furthermore, we found that dentin matrix protein 1 (DMP1), which is a direct downstream molecular of ER, was involved in 17β-estradiol/ER pathway-regulated osteogenesis. As well, glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signal pathway also participates in ERα/β/DMP1-regulated chondrocyte osteogenesis. The GSK-3β/β-catenin signal pathway was involved in ERα/β/DMP1-regulated chondrocyte osteogenesis. These findings suggest that ER/DMP1/GSK-3β/β-catenin plays a vital role in estrogen regulation of chondrocyte osteogenesis and provide a therapeutic target for short stature caused by epiphyseal fusion.”