Here’s the last LSJL update.  Here’s the feet images from the this time which have had the best results out of what I’ve been clamping:

The size increase is not due to flattening of the arches as the arch on the right foot actually looks bigger.  You’ll note that the second and third toe look bigger as well.  My wingpsan has increased from 74.5″ to 74.75″ up from the 72.5″ it was before I started LSJL.  It is very difficult however to take a good wingspan picture.

Part of the trouble with LSJL has been slipping when clamping and a possible solution is that rather than clamping the epiphysis of the bone is to clamp the neck of the bone.

Considering the spillover of the second and third toe growth, I’d say it’s probably more important to generate clamping force than it is to be at the optimal location.  Clamping at the neck of the bone also clamps the muscle as well which result in more fluid flowing into the bone.  Also clamping at the neck of the bone gets closer to the bone marrow and one key conclusion I’ve come to my LSJL research so far is that the cortical bone and the outer periosteum(growth in width is difficult as well as growth in length) inhibit bone growth and inner periosteum and bone marrow stimulate bone growth.  Distraction osteogenesis both gets rid of cortical bone via fracture and stimulates the bone marrow via blood clot.

By continuing to clamp the epiphysis of the bone is likely the reason why my length gains plateaued as whenever I tried to increase the clamping force the clamp would slip off.  By clamping the neck of the bone I can continue to increase the clamping force without having to worry about slippage.  Hopefully, this will allow me to get some leg length increases that I’ll be able to report otherwise I’ll see if I can continue to gain in the feet and that’ll be proof of concept that I can use to gain more resources to establish better clamping technology to gain in the legs.

I bought a new clamp for my fingers as the standard six inch clamp was just too big.

The problem with this is all the holes in the clamp that make clamping uncomfortable.  If neck clamping with the Irwin Quick Grip clamp doesn’t work

I can doing the C-class clamp again but I worry even with clamping the neck of the bone rather than the epiphysis there’ll be too much slipping.

We’ll see what happens in one to two weeks.  And if it doesn’t seem to be working I’ll switch it up.  Considering my foot growth if I don’t observe results in a reasonable time frame then it’s time to switch things up

I tried hand clamping but I seemed to plateau with it so I’m back to using the C-class but more intensely than before.  Here is me doing some bones with a C-class clamp.  I’ve been getting some progress with my feet at least but that could be because changes in the feet are more noticeable because my shoes feel more snug.  Here’s the last feet images I took for comparison.  The first image there is actually the before picture.  Also the II phalanxes(toe closest to big toe) seems longer as well which makes sense since I’m clamping close by.

But my feet seemed to go up in size very quickly once I change methodology of using the C-class clamp over the hand clamp.  So if there’s no changes in a week then I will try something different.  Michael thought about using two C-class clamps at once.  Ideally, yes you want to gain height but the feet is where I’m getting results and if my right shoe no longer fits that would be hard to deny proof and I could use that proof to acquire more resources to translate to height increase research.

Since the II toe is growing I’m worried less about a precise clamping location and more about clamping force.  Now it is possible that the feet could be flattening but the big toe is already pretty straight.  Well if I can keep getting results than such minutiae won’t matter.

Here’s pictures of my feet:

The right toe is bigger.  I’m not to the point where I need to go up a size for my right foot but I’m closer.

Here’s some unilaterally swollen feet:  The bones don’t physically look longer.  So I don’t think it’s swelling making my feet appear longer.

Here’s another unilaterally swollen foot:

Here’s another:

This study basically explains that macrophages are key to neo-endochondral ossification:

Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early endochondral ossification.

“The distribution, phenotype, and requirement of macrophages for fracture-associated inflammation and/or early anabolic progression during endochondral callus formation were investigated. A murine femoral fracture model [internally fixed using a flexible plate (MouseFix)] was used to facilitate reproducible fracture reduction. IHC demonstrated that inflammatory macrophages (F4/80(+)Mac-2(+)) were localized with initiating chondrification centers and persisted within granulation tissue at the expanding soft callus front. They were also associated with key events during soft-to-hard callus transition. Resident macrophages (F4/80(+)Mac-2(neg)), including osteal macrophages, predominated in the maturing hard callus. Macrophage Fas-induced apoptosis transgenic mice were used to induce macrophage depletion in vivo in the femoral fracture model. Callus formation was completely abolished when macrophage depletion was initiated at the time of surgery and was significantly reduced when depletion was delayed to coincide with initiation of early anabolic phase. Treatment initiating 5 days after fracture with the pro-macrophage cytokine colony stimulating factor-1 significantly enhanced soft callus formation. The data support that inflammatory macrophages were required for initiation of fracture repair, whereas both inflammatory and resident macrophages promoted anabolic mechanisms during endochondral callus formation. Overall, macrophages make substantive and prolonged contributions to fracture healing and can be targeted as a therapeutic approach for enhancing repair mechanisms. Thus, macrophages represent a viable target for the development of pro-anabolic fracture treatments with a potentially broad therapeutic window.”

“inflammatory macrophages were required for initiation of fracture repair, whereas both inflammatory and resident macrophages promoted anabolic mechanisms during endochondral callus formation.”

“Periosteal endochondral callus formation progresses via four sequential and interdependent phases: inflammation leading to granulation tissue formation, early anabolism (soft cartilaginous callus formation), late anabolism (hard bony callus formation), and remodeling to reinstate the original bone architecture and mechanical strength”

“recruited inflammatory macrophages are derived from blood monocytes and rapidly infiltrate tissues compromised by injury, abnormal function, and/or infection”

“Inflammatory macrophages predominate in fracture granulation tissue and associate with chondrification centers. Representative images of periosteal fracture zone (Supplemental Figure S1A) 7 days after osteotomy and MouseFix plate fixation surgery in 12-week-old C57Bl/6 mice (n = 6 with assessment at multiple sectional depths per sample). All sections were counterstained with hematoxylin. A: Image represents approximately half of the periosteal fracture zone (proximal) with the osteotomy-generated fracture gap (FG) at the bottom left of the image. Granulation tissue predominates at this time point. Tissue section was stained by IHC for the F4/80 pan-macrophage antigen (brown). The black box demarks the region shown in B and C. The blue box demarks the region shown in E and F. B: IHC for F4/80 expression within fracture granulation tissue. The dashed line demarks the interface between the mesenchymal (closest to bone, below dashed line) and inflammatory (above dashed line) stratum. F4/80+ cells with stellate morphological characteristics are evident in both the inflammatory and mesenchymal (arrows) strata. The circle demarks a single osteomac within this field. C: IHC for Mac-2 expression (brown) in a serial section to that shown in B. Arrows point to the same cells indicated in B and highlight the high degree of overlap in F4/80 (B) and Mac-2 (C) staining patterns. The circle indicates the Mac-2neg osteomac identified in B. D: Quantification of the number of F4/80+ and macrophage-like Mac-2+ cells within the mesenchymal stratum of the granulation tissue. An average area of 0.15 mm2 was assessed in six independent samples, and the number of positive cells was not statistically different. E: F4/80+ macrophages (brown, arrows) adjacent to a periosteal chondrification center. F: Mac-2 staining in a serial section to E confirms induction of Mac-2 expression in condensing chondrocyte-like cells within the periosteal chondrification center (blue boxed area). The same F4/80+ macrophages noted in E can be traced and express Mac-2 (arrows). Dashed line in B, C, E, and F demarks the mesenchymal (lower)- inflammation (upper) strata junction within the granulation tissue. Original magnifications: ×10 (A), ×40 (B and C); ×60 (E and F). Scale bars: 100 μm (A); 50 μm (B and C); 37.5 μm (E and F).”

“chondroblasts were identified as F4/80negMac-2+ condensed mesenchymal cells (Figure 1F). F4/80+Mac-2+ (Figure 1, E and F) inflammatory macrophages were observed adjacent to chondrification centers and associated vascular structures.”

” Cartilage and woven bone formations were absent within the periosteal fracture zone [with no macrophages]”

Macrophages are also present in the soft to hard callus transition although this is not as important for purposes as creating the initial growth plate is the limiting factor.

” inflammatory macrophages [were present] in the mesenchymal stratum of the granulation tissue, including some that were associated with developing chondrification centers”

“The developmental vascular canals were broad invaginations with osteoclasts/chondroclasts at the apical tip, presumably excavating the canal path via matrix degradation, followed by a mixture of mesenchymal cells, osteoclasts/chondroclasts, lysosomal cells, macrophages, and endothelial cells.”

“macrophages are pro-mitogenic toward chondrocytes.”<-macrophages undergo chondrocytes to undergo cell division.

Resting and injury-induced inflamed periosteum contain multiple macrophage subsets that are located at sites of bone growth and regeneration.

“Better understanding of bone growth and regeneration mechanisms within periosteal tissues will improve understanding of bone physiology and pathology. Macrophage contributions to bone biology and repair have been established but specific investigation of periosteal macrophages has not been undertaken. We used an immunohistochemistry approach to characterise macrophages in growing murine bone and within activated periosteum induced in a mouse model of bone injury. Osteal tissue macrophages (osteomacs) and resident macrophages were distributed throughout resting periosteum. Tissues were collected from 4 week old mice and osteomacs were observed intimately associated with sites of periosteal diaphyseal and metaphyseal bone dynamics associated with normal growth. This included F4/80+Mac-2-/low osteomac association with extended tracks of bone formation (modeling) on diphyseal periosteal surfaces. While this recapitulated endosteal osteomac characteristics, there was subtle variance in the morphology and spatial organization of modelling-associated osteomacs, which likely reflects the greater structural complexity of periosteum. We also demonstrated that osteomacs, resident macrophages and inflammatory macrophages (F4/80+Mac-2hi) were associated with the complex bone dynamics occurring within the periosteum at the metaphyseal corticalization zone. These 3 macrophage subsets were also present within activated native periosteum after bone injury across a 9 day time course that spanned the inflammatory through remodeling bone healing phases. This included osteomac association with foci of endochondral ossification within the activated native periosteum. These observations confirm that osteomacs are key components of both osteal tissues, in spite of salient differences between endosteal and periosteal structure and that multiple macrophage subsets are involved in periosteal bone dynamics”

“The periosteum is a specialized connective tissue composed of a vascularized and innervated fibrous membrane that encapsulates bone. It has two layers: an outer fibrous capsule layer containing elastic connective tissue (including Sharpey’s fibres), fibroblasts and blood vessels; and, an inner cambium layer containing capillaries, nerves, pre-osteoblasts/bone lining cells, osteoblasts and undifferentiated mesenchymal stromal/stem cells (also referred to as periosteum-derived progenitor cells)”<-these stem cells could potentially be involved in neo growth plate formation.

“Progenitor cells within the endosteum and periosteum have different potential: endosteal progenitors are restricted to osteoblastic differentiation but periosteal progenitors have osteoblastic and chondrocytic bi-potential.”<-It isn’t necessarily true that endosteal progenitors are restricted to osteoblast differentiation it could be influenced by the microenvironment.

Macrophages in bone fracture healing: Their essential role in endochondral ossification.

“In fracture healing, skeletal and immune system are closely interacting through common cell precursors and molecular mediators. It is thought that the initial inflammatory reaction, which involves migration of macrophages into the fracture area, has a major impact on the long term outcome of bone repair. Interestingly, macrophages reside during all stages of fracture healing. Thus, we hypothesized a critical role for macrophages in the subsequent phases of bone regeneration. This study examined the impact of in vivo induced macrophage reduction, using clodronate liposomes, on the different healing phases of bone repair in a murine model of a standard closed femoral fracture. A reduction in macrophages had no obvious effect on the early fracture healing phase, but resulted in a delayed hard callus formation, thus severely altering endochondral ossification. Clodronate treated animals clearly showed delayed bony consolidation of cartilage and enhanced periosteal bone formation. Therefore, we decided to backtrack macrophage distribution during fracture healing in non-treated mice, focusing on the identification of the M1 and M2 subsets. We observed that M2 macrophages were clearly prevalent during the ossification phase. Therefore enhancement of M2 phenotype in macrophages was investigated as a way to further bone healing. Induction of M2 macrophages through interleukin 4 and 13 significantly enhanced bone formation during the 3week investigation period. These cumulative data illustrate their so far unreported highly important role in endochondral ossification and the necessity of a fine balance in M1/M2 macrophage function, which appears mandatory to fracture healing and successful regeneration.”

The failure of endochondral ossification was macrophage specific and not indirectly related to osteoclasts.  Osteoclasts and macrophages come from the same progenitor cell.

Myxedema increases hydrostatic pressure by resulting in increased deposition of connective tissue elements like hyaluronic acid and GAGS(chondroitin).  Maybe there’s a way to use the pathology of this disease to safely increase the deposition of connective tissue to possibly increase height.

Increases in deposition of this elements can result from scar tissue.  Perhaps the separation in limb lengthening surgery can be thought of as a form of scar.  Increases in Fibroblast levels also could increase accumulation of connective tissue.  It is worth it to note that FGFR3 decreases height.  Maybe an interesting possibility is that FGFR3 reduces circulation Fibroblast levels and decreases hydrostatic pressure and results in a height increase that way. Thyroid hormone is thought to increase these connective tissue elements.

Maybe in pregnancy the elevated thyroid causes the bump in the stomach during pregnancy and possibly causes the increase in shoe size and height.  Being pregnant can increase the size and production of the thyroid.

Actors like Marty Feldman who had graves disease was not tall at 5’7″.

Other famous with Graves:

Missy Elliott-F 5’2″

Rodney Dangerfield-M 5’10”

1st President Bush-M 6’2″

Maggie Smith-F 5’5″

According to this paper Graves’ disease–acceleration of linear growth., Grave’s may cause an acceleration of linear growth but I could not find anymore beyond the title.

Body height and weight of patients with childhood onset and adult onset thyrotoxicosis.<-Thyrotoxisis is another name for hyperthyroidism

“The present study has compared body height and weight of thyrotoxic female patients of childhood onset and adult onset. The body height of 141 out of 143 (99%) adult-onset thyrotoxic patients was within the range of mean +/- 2SD for the age-matched general Japanese female population. On the other hand, in 42 patients with childhood-onset thyrotoxicosis, 6 (14%) had their height being greater than the mean + 2SD of general population, and 34 (81%) were taller than the mean value. In 86 patients with siblings, 42 (49%) were at least 2 cm taller than their sisters, and 26 (30%) were more than 2 cm shorter than their sisters. The body weight of 27 out of 42 (68%) patients younger than 20 years was not decreased but was even greater than the mean value for the age-matched general population. The results indicate that excessive thyroid hormone in vivo enhances body height in humans. The increased body weight in some young patients suggests that enhanced dietary intake due to increased appetite in hyperthyroidism has overcome the energy loss with increased metabolism.”

If you look at figure 1 you get quite a interesting figure that shows that of females with adult onset hyperthyroidism tend to be taller than the mean(this is not a longitudinal study so hyperthyroidism could not be a direct measurement of height increase).  I could not excise the figure out of the study you will have to look at it directly.

46, XY pure gonadal dysgenesis: a case with Graves’ disease and exceptionally tall stature.

“Growth was arrested with height remaining at 187 cm after normalization of the thyroid function by treatment with an antithyroid agent, although follow-up to monitor growth was limited to 3 months. In some cases of gonadal dysgenesis, then, Graves’ disease may contribute to an abnormally tall stature.”

So we see that Grave’s disease has an impact on height but that the affect on height is variable sometimes an increase and sometimes a decrease.  Maybe there’s some other variable like FGFR3 levels that influence the effects on height.

This provides more evidence that hydrostatic pressure influences height but perhaps some other stimuli is needed like CNP as increases Fibroblastic stimuli would result in more FGFR3 stimuli in some cases.  CNP would cancel that out.

Tubacin is not over the counter but you can buy it but it’s for lab research only so there’s no guarantee that it’ll work and we don’t know if there’s side effects.  “Tubacin is a highly potent and selective, reversible, cell-permeable HDAC6 inhibitor with an IC50 of 4 nM in a cell-free assay, approximately 350-fold selectivity over HDAC1.”

HDAC6 deficiency or inhibition blocks FGFR3 accumulation and improves bone growth in a model of achondroplasia.

“Mutations that cause increased and/or inappropriate activation of FGFR3 are responsible for a collection of short-limbed chondrodysplasias. These mutations can alter receptor trafficking and enhance receptor stability, leading to increased receptor accumulation and activity.  wildtype and mutant activated forms of FGFR3 increase expression of the cytoplasmic deacetylase HDAC6 (Histone Deacetylase 6) and that FGFR3 accumulation is compromised in cells lacking HDAC6 or following treatment of fibroblasts or chondrocytes with small molecule inhibitors of HDAC6. The reduced accumulation of FGFR3 was linked to increased FGFR3 degradation that occurred through a lysosome-dependent mechanism. Using a mouse model of Thanatophoric Dysplasia Type II (TDII) we show that both HDAC6 deletion and treatment with the small molecule HDAC6 inhibitor tubacin reduced FGFR3 accumulation in the growth plate and improved endochondral bone growth. Defective endochondral growth in TDII is associated with reduced proliferation and poor hypertrophic differentiation and the improved bone growth was associated with increased chondrocyte proliferation and expansion of the differentiation compartment within the growth plate.”

“The effects of activating FGFR3 mutations on growth plate chondrocytes are mediated by the activation or modulation of several interconnected downstream signaling programs, including the MAPK, BMP and Hedgehog pathways. These pathways converge on key downstream targets such as STAT, SMAD, Snail and Sox9 transcription factors that play important roles in chondrocyte proliferation, differentiation and survival”

“HDAC6 controls FGFR3 accumulation by regulating its protein stability and that tubacin-dependent destabilization of FGFR3 is more robust in chondrocytes than in MEFs.”

“the absence of HDAC6 resulted in modest increases in tibia and femur OB length, but not in ulna or humerus”

” since HDAC6 regulates FGFR3 accumulation, increased HDAC6 might trigger a positive feedback system whereby HDAC6 and FGFR3 promote and maintain each other’s expression. Elevated FGFR3 in this scenario is predicted to behave analogously to mutant versions of FGFR3 and have a negative effect on both chondrocyte proliferation and differentiation. In addition or alternatively, elevated HDAC6 in achondrodysplasia-related disorders might contribute to disease by deacetylation of proteins such as α−Tubulin and Cortactin which can alter cell mobility and adhesion ”

Requirement of HDAC6 for activation of Notch1 by TGF-β1.

“TGF-β1 is enriched in the tumor microenvironment and acts as a key inducer of epithelial to mesenchymal transition (EMT) {Mesenchymal to Epithelial translation may be a key growth plate stage but knowledge of the reverse may be important to our understanding} in lung cancer. The NOTCH signaling pathway is conserved across species and is an essential pathway for development, cell differentiation, and cancer biology. Dysregulation of Notch signaling is a common feature of non-small cell lung cancer (NSCLC) and is correlated with poor prognosis. Crosstalk exists between the NOTCH and TGF-β signaling pathways in EMT. Herein we report that histone deacetylase 6 (HDAC6) modulates TGF-β1-mediated activation of the Notch pathway. HDAC6, a primarily cytoplasmic deacetylase, mediates TGF-β1-induced EMT in human lung cancer cells. Inhibition of HDAC6 with a small molecule inhibitor, namely tubacin or with siRNA attenuated TGF-β1-induced Notch-1 signaling. We show that TGFβ-1-induced EMT is accompanied by rapid HDAC6-dependent deacetylation of heat shock protein 90 (HSP90). Consistently, inhibition of HSP90 with its small molecule inhibitor 17AAG attenuated expression of TGF-β1-induced Notch-1 target genes, HEY-1 and HES-1. These findings reveal a novel function of HDAC6 in EMT via mediating the TGF-β-Notch signaling cascade, and support HDAC6 as a key regulator of TGFβ-induced EMT in NSCLC.”

“Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells lose their characteristic cell-cell junctions and polarization of cell-surface molecules while acquiring properties typical of mesenchymal cells”

Some supplements affect MMP expression.  Zinc suppresses MMP2 and MMP9(Zinc Regulates Lipid Metabolism and MMPs Expression in Lipid Disturbance Rabbits.) and Selenium decreases MMP2 and TIMP1 levels(Selenium’s effects on MMP-2 and TIMP-1 secretion by human trabecular meshwork cells).

Effects of matrix metalloproteinases on the fate of mesenchymal stem cells.

“Mesenchymal stem cells (MSCs) have great potential as a source of cells for cell-based therapy because of their ability for self-renewal and differentiation into functional cells. Moreover, matrix metalloproteinases (MMPs) have a critical role in the differentiation of MSCs into different lineages. MSCs also interact with exogenous MMPs at their surface, and regulate the pericellular localization of MMP activities{so you could supplement with exogenous(external from the body) MMPs to manipulate MSC and hopefully induce chondrogesis}. The fate of MSCs is regulated by specific MMPs associated with a key cell lineage.  MMPs [are integrated] in the differentiation, angiogenesis, proliferation, and migration of MSCs{all these four things are likely factors related to chondroinduction}. These interactions are not fully understood and warrant further investigation, especially for their application as therapeutic tools to treat different diseases. Therefore, overexpression of a single MMP or tissue-specific inhibitor of metalloproteinase in MSCs may promote transdifferentiation into a specific cell lineage{this could help you grow taller if it’s transdifferentiation towards a chondrogenic lineage the official term for neo growth plate formation would be something like interosseous chondrofication}, which can be used for the treatment of some diseases. In this review, we critically discuss the identification of various MMPs and the signaling pathways that affect the differentiation, migration, angiogenesis, and proliferation of MSCs.”

“Collagenases (MMP-1, MMP-8, MMP-13, and MMP-18) cleave fibrillar collagen types I, II, and III, and they can cleave other ECM proteins. Gelatinases (MMP-2 and MMP-9) have high activity against gelatin, and degrade other ECM molecules including collagens, laminin, and aggrecan. Stromelysins (MMP-3, MMP-10, and MMP-11) digest a number of noncollagen ECM molecules, and their domain arrangement is similar to that of collagenases. The membrane-type MMPs (MT-MMPs) (MMP-14, MMP-15, MMP-16, MMP-17, MMP-24, and MMP-25) are intracellularly activated transmembrane molecules, and their active forms are expressed on the cell surface. There are other less characterized members including MMP-7, MMP-12, MMP-19, MMP-20, MMP-22, and MMP-23”

“MMPs have critical role in the differentiation of MSCs to adipocytes, osteocytes, and chondrocytes. MSCs interact with exogenous MMPs at their surface and activate proMMP-2 and proMMP-13, regulating the pericellular localization of MMP activities. They have the capability to regulate exogenous MMP-2 and MMP-9 by the expression of TIMP-2 and TIMP-1, protecting the perivascular niche from their high levels”

“silencing of MMP-2 by siRNA impaired chondrogenic differentiation, and increased the protein level of fibronectin and β1 integrin. Treatment with a MMP-2 activator resulted in the activation of chondrogenesis. ”

“MMP-2 is involved in the chondrogenic differentiation of MSCs via downregulation of focal adhesion kinase (FAK)–β1 integrin interaction, which leads to phosphorylation of FAK”

“the degradation of MMPs enhances the chondrogenic differentiation of MSCs by allowing the morphological changes and increasing the contents of glycosaminoglycans (GAG) and expression of chondrogenic markers. A chondrogenic cell line (ATDC5) was examined for chondrogenic differentiation, and the expression of MMP-2, MMP-9, and MT1-MMP was upregulated during the early stages of chondrogenic differentiation with a downregulation in the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK)”

“t the increase in production of MMP-13 drives the MSC differentiation to chondrocytes by degrading the cleavable components of the ECM, and regulating integrin-binding peptides”

“Stimulation of MSCs in chondrogenic media with IL-β1 resulted in increased expression of MMP-2, MMP-3, and MMP-13 while IL-6 downregulated the expression of MMP-3 and MMP-13 compared with control without stimulation”

” Commitment of MSCs to differentiate into a specific lineage, proliferate, or migrate is regulated by many factors in the local tissue microenvironment.”<-So finding a way to stimulate MMP2 on it’s own may not be enough on it’s own to create chondroinduction.