Natural Height Increase with Creatine

Previously, we read about how inhibiting F-spondin can increase height.  F-spondin increases MMP levels, TGF-Beta levels, FGF, platelet-derived growth factor levels, and hepatic growth factor levels.  One of the members of the TGF-Beta super family is Myostatin(or GDF-8).  TGF-Beta is used to promote differentiation into chondrocytes and osteoblasts(although sometimes Bone Morphogenic Proteins can be used) so it is absolutely needed.  But there are several cellular proliferation inhibiting mechanisms of TGF-Beta including Myostatin.  But since TGF-Beta promotes cellular differentiation so effectively it is superior for us to target the catabolic genes or counteract the catabolic effects(such as taking Astragalus due to effect TGF-Beta has on shortening telomeres).  Creatine may inhibit Myostatin and therefore may be a potent way for natural height increase.  Creatine is readily available: Optimum Nutrition Creatine Powder, 600g

First, let's discuss GASP-1:

Regulation of myostatin in vivo by GASP-1: a novel protein with protease inhibitor and follistatin domains

"Myostatin, a member of the TGF\- superfamily, is a potent and specific negative regulator of skeletal muscle mass. In serum, myostatin circulates as part of a latent complex containing myostatin propeptide and/or follistatin-related gene (FLRG).  GDF-associated serum protein-1 (GASP-1), contains multiple domains associated with protease inhibitory proteins, including a WAP domain, a Kazal domain, two Kunitz domains, and a netrin domain [is associated with endogenous myostatin in normal mouse and human serum]. GASP-1 also contains a domain homologous to the 10-cysteine repeat found in follistatin, a protein that binds and inhibits activin, another member of the TGF\- superfamily. We have cloned mouse GASP-1 and shown that it inhibits the biological activity of mature myostatin, but not activin. Recombinant GASP-1 binds directly not only to mature myostatin, but also to the myostatin propeptide."

Note that Netrin is involved in axonal guidance providing a link between it and F-spondin which modifies axons.  GASP-1 may inhibit Netrin and thereby inhibit commissural axon outgrowth.  Now by inhibiting F-spondin you are also inhibiting commisural axon outgrowth.  Perhaps, commisural outgrowth of motor axons results in growth reduction.

The other effect of GASP-1 is that it inhibits protease.  Protease breaks down peptide bonds that link amino acids together which means that it can break down compounds like Human Growth Hormone(growth hormone is peptide based)!

"Myostatin RNA is produced nearly exclusively in skeletal muscle[so muscular exercise may help bone growth by inhibiting myostatin]. To determine the tissue distribution of GASP-1 mRNA, a 551-bp fragment of GASP-1 was amplified from first-strand cDNA produced from a variety of mouse tissues and staged embryos. GASP-1 appears to be fairly widely expressed, with particularly high expression in skeletal muscle and heart. Significant expression is also seen in brain, lung, and testis. In contrast, liver and kidney express relatively low levels of GASP-1 mRNA. Developmentally, the level of GASP-1 mRNA remains fairly constant, perhaps increasing slightly between d 7 and d 11 of mouse embryogenesis[GASP-1 doesn't seem to be expressed(or at least not as much to mention) in bone, thus again muscular exercise may be needed to stimulate the effects of GASP-1, and the muscular production of GASP-1 may be stimulatory on bone]."

So, muscular exercise has stimulatory effects on height increase by inhibiting myostatin and stimulatory effects on GASP-1 which could be a negative feedback mechanism on HGH by degrading peptide bonds.

"GASP-1 inhibited the activity of BMP-11"<-BMP-11 is very similar to Myostatin genetically but BMP-11 seems to be more necessary than Myostatin.  In the study, they managed to inhibit Myostatin exclusively with the IC50 domain but it's unclear whether collateral inhibition of BMP-11 by GASP-1 will be detrimental and whether development will be fine with reduced but not inhibited levels of BMP-11.

Effects of oral creatine and resistance training on serum myostatin and GASP-1

"[We] determine the effect of resistance training for 8 weeks in conjunction with creatine supplementation on muscle strength, lean body mass, and serum levels of myostatin and growth and differentiation factor-associated serum protein-1 (GASP-1). In a double-blinded design 27 healthy male subjects (23.42 ± 2.2 years) were assigned to control (CON), resistance training + placebo (RT + PL) and resistance training + creatine supplementation (RT + CR) groups. The protocol consisted of 3 days per week of training for 8 weeks, each session including three sets of 8–10 repetitions at 60–70% of 1 RM for whole-body exercise. Blood sampling, muscular strength testing and body composition analysis (full body DEXA) were performed at 0, 4th and 8th weeks. Myostatin and GASP-1 was measured. Resistance training caused significant decrease in serum levels of myostatin and increase in that of GASP-1. Creatine supplementation in conjunction with resistance training lead to greater decreases in serum myostatin, but had no additional effect on GASP-1. The effects of resistance training on serum levels of myostatin and GASP-1, may explain the increased muscle mass that is amplified by creatine supplementation."

Creatine can make you taller by inhibiting myostatin.  Exercise can make you taller by inhibiting myostatin and increasing serum levels of GASP-1 which in turn inhibits Myostatin further.  GASP-1 can also prevent the breakdown of anabolic hormones like HGH.  Lower serum levels of myostatin means lower levels of myostatin for the growth plate.  Creatine also may be superior to exercise as GASP-1 additionally inhibits BMP-11 which is needed for proper development.

Activin IIRB is expressed in chondrocytes and the periosteum. "Myostatin mediates its actions through binding to activin IIb receptors"<-So again myostatin has an effect on bone but the main inhibitory factors on myostatin occur with muscle.

"Subjects assigned to the RT + CR group received creatine monohydrate in capsule form (Gensan Abiogen Pharama; Italy) at a dose 0.3 g kg−1 day−1 (divided into three equal doses) for the 1st week (loading period) and 0.05 g kg−1 day−1 (once daily) for the remaining 7 weeks. This supplementation protocol was anticipated to increase muscle creatine levels by 14–28%"<-The dosages used.  Creatine inhibits myostatin production of the muscle which has effects on all cell types.

Creatine and Resistance training combined decreased serum levels of Myostatin by about 1/6th(120ng/ml to 100 ng/ml) over 8 weeks.  Resistance Training on it's own increased levels of GASP-1 more than Resistance Training plus creatine.  Thus, Creatine helped selectively inhibit Myostatin while avoiding GASP-1 induced inhibition of BMP-11.

Creatine would seem to be optimized for height increase during development and during a height increase program like LSJL.

Inhibiting Myostatin to increase your Height

We know it's possible to grow taller by inhibiting myostatin.  But how do we inhibit myostatin?  Myostatin helps regulate stem cell proliferation and differentiation(it inhibits it).  If we could inhibit myostatin we would benefit from enhanced stem cell proliferation and differentiation.  If you are doing Lateral Synovial Joint Loading, you want as much MSC proliferation and differentiation as possible.  If you are still naturally developing then inhibiting myostatin and nothing else may help you increase your stature. There are no products out right now that inhibit myostatin.  Are there natural ways to inhibit myostatin?  Can we design exercises? 

Caveolin-3 regulates myostatin signaling. Mini-review.

"Caveolins, components of the uncoated invaginations of plasma membrane, regulate signal transduction and vesicular trafflicking. Loss of caveolin-3, resulting from dominant negative mutations of caveolin-3 causes autosomal dominant limb-girdle muscular dystrophy (LGMD) 1C and autosomal dominant rippling muscle disease (AD-RMD). Myostatin, a member of the muscle-specific transforming growth factor (TGF)-beta superfamily, negatively regulates skeletal muscle volume[It negatively regulates bone volume too]. Herein we review caveolin-3 suppressing of activation of type I myostatin receptor, thereby inhibiting subsequent intracellular signaling. In addition, a mouse model of LGMD1C has shown atrophic myopathy with enhanced myostatin signaling. Myostatin inhibition ameliorates muscular phenotype in the model mouse, accompanied by normalized myostatin signaling. Enhanced myostatin signaling by caveolin-3 mutation in human may contribute to the pathogenesis of LGMD1C. Therefore, myostatin inhibition therapy may be a promising treatment for patients with LGMD1C. More recent studies concerning regulation of TGF-beta superfamily signaling by caveolins have provided new insights into the pathogenesis of several human diseases." 

Now remember that TGF-beta is important in causing stem cells to differentiate into chondrocytes.  This means that caveolins are very important.  Caveolin-3 actually supresses myostatin reception.  Extraneous injection of Caveolin-3 may inhibit myostatin and increase stem cell differentiation.   

Here's a way to inhibit myostatin if you haven't been born yet... 

Myostatin gene knockdown through lentiviral-mediated delivery of shRNA for in vitro production of transgenic bovine embryos. 

"Myostatin is described as a negative regulator of the skeletal muscle growth. Genetic engineering, in order to produce animals with double the muscle mass and that can transmit the characteristic to future progeny, may be useful. In this context, the present study aimed to analyse the feasibility of lentiviral-mediated delivery of short hairpin RNA (shRNA) targeting of myostatin into in vitro produced transgenic bovine embryos. Lentiviral vectors were used to deliver a transgene that expressed green fluorescent protein (GFP) and an shRNA that targeted myostatin. Vector efficiency was verified through in vitro murine myoblast (C2C12) cell morphology after inductive differentiation and by means of real-time PCR. The lentiviral vector was microinjected into the perivitellinic space of in vitro matured oocytes. Non-microinjected oocytes were used as the control. After injection, oocytes were fertilized and cultured in vitro. Blastocysts were evaluated by epifluorescence microscopy. Results demonstrated that the vector was able to inhibit myostatin mRNA in C2C12 cells, as the transducted group had a less amount of myostatin mRNA after 72 h of differentiation (p < 0.05) and had less myotube formation than the non-transduced group (p < 0.05). There was no difference in cleavage and blastocyst rates between the microinjected and control groups. After hatching, 3.07% of the embryos exhibited GFP expression, indicating that they expressed shRNA targeting myostatin. In conclusion, we demonstrate that a lentiviral vector effectively performed shRNA myostatin gene knockdown and gene delivery into in vitro produced bovine embryos. Thus, this technique can be considered a novel option for the production of transgenic embryos and double muscle mass animals." 

Now it's possible to alter gene expression in fully developed adults too.  So perhaps this lentiviral vector can be used to alter stature in people already born.  

We can also block myostatin signaling... 

SB431542 treatment promotes the hypertrophy of skeletal muscle fibers but decreases specific force. 

"The small molecule inhibitor SB431542 inhibits activin type I receptors. The muscle growth-inhibitor myostatin binds to and signals via these receptors. The aim of this study was to test the hypothesis that SB431542 can inhibit myostatin-related Smad signaling and induce muscle growth in cultured C2C12 myotubes and increase growth and specific force in cultured Xenopus muscle fibers. The effect of SB431542 was assessed in vitro on C2C12 myotubes and ex vivo using mature Xenopus muscle fibers. SB431542 treatment reduced myostatin-induced C-terminal Smad2 phosphorylation and resulted in the formation of enlarged myotubes. However myogenin expression was unchanged, while p70 S6k phosphorylation at Thr389, total myosin heavy chain, and the rate of protein synthesis were all reduced. Mature Xenopus muscle fibers that were treated with SB431542 had a higher fiber cross-sectional area but decreased specific force production than control. SB431542 can initially antagonize myostatin signaling, but long-term unexpected signaling effects occur. Muscle fibers hypertrophy, but their specific force decreases compared to control." 

Two problems:  SB431542 did not have long-term benefits and we need to inhibit myostatin's effects in the bone not the muscle.  

Extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway is involved in myostatin-regulated differentiation repression. 

"The cytokines of transforming growth factor beta (TGF-beta) and its superfamily members are potent regulators of tumorigenesis and multiple cellular events. Myostatin is a member of TGF-beta superfamily and plays a negative role in the control of cell proliferation and differentiation. We now show that myostatin rapidly activated the extracellular signal-regulated kinase 1/2 (Erk1/2) cascade in C2C12 myoblasts. A more remarkable Erk1/2 activation stimulated by myostatin was observed in differentiating cells than proliferating cells. The results also showed that Ras was the upstream regulator and participated in myostatin-induced Erk1/2 activation because the expression of a dominant-negative Ras prevented myostatin-mediated inhibition of Erk1/2 activation and proliferation. Importantly, the myostatin-suppressed myotube fusion and differentiation marker gene expression were attenuated by blockade of Erk1/2 mitogen-activated protein kinase (MAPK) pathway through pretreatment with MAPK/Erk kinase 1 (MEK1) inhibitor PD98059, indicating that myostatin-stimulated activation of Erk1/2 negatively regulates myogenic differentiation. Activin receptor type IIb (ActRIIb) was previously suggested as the only type II membrane receptor triggering myostatin signaling. In this study, by using synthesized small interfering RNAs and dominant-negative ActRIIb, we show that myostatin failed to stimulate Erk1/2 phosphorylation and could not inhibit myoblast differentiation in ActRIIb-knockdown C2C12 cells, indicating that ActRIIb was required for myostatin-stimulated differentiation suppression. Altogether, our findings in this report provide the first evidence to reveal functional role of the Erk1/2 MAPK pathway in myostatin action as a negative regulator of muscle cell growth." 

So inhibiting ActRIIb can also enhance cellular proliferation as can inhibiting Ras. 

Enhanced muscle growth by plasmid-mediated delivery of myostatin propeptide. 

"Myostatin is a member of the transforming growth factor beta (TGF-beta) superfamily that functions as a negative regulator of skeletal muscle development and growth. Myostatin blockade therefore offers a strategy for promoting muscle growth in livestock production without resorting to genetic manipulation. In this report, we examined the effect of myostatin inhibition by plasmid-mediated delivery of a mutant myostatin propeptide (MProD76A), a natural inhibitor of myostatin, on the growth performance of mice. A significant increase in skeletal muscle mass was observed after a single intramuscular injection of naked plasmid DNA encoding MProD76A into mice. Enhanced muscle growth occurred because of myofiber hypertrophy, but no cardiac muscle hypertrophy and organomegaly was observed in the mice after myostatin inhibition by plasmid-mediated MProD76A delivery. These results demonstrate a promising approach to enhancing muscle growth that warrants further investigation in domestic animals." 

Now this peptide may only inhibit myostatin in myofiber muscle and not bone.  

Systemic myostatin inhibition via liver-targeted gene transfer in normal and dystrophic mice. 

"Myostatin inhibition is a promising therapeutic strategy to maintain muscle mass in a variety of disorders, including the muscular dystrophies, cachexia, and sarcopenia. Previously described approaches to blocking myostatin signaling include injection delivery of inhibitory propeptide domain or neutralizing antibodies. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a unique method of myostatin inhibition utilizing recombinant adeno-associated virus to overexpress a secretable dominant negative myostatin exclusively in the liver of mice. Systemic myostatin inhibition led to increased skeletal muscle mass and strength in control C57 Bl/6 mice and in the dystrophin-deficient mdx model of Duchenne muscular dystrophy. The mdx soleus, a mouse muscle more representative of human fiber type composition, demonstrated the most profound improvement in force production and a shift toward faster myosin-heavy chain isoforms. Unexpectedly, the 11-month-old mdx diaphragm was not rescued by long-term myostatin inhibition. Further, mdx mice treated for 11 months exhibited cardiac hypertrophy and impaired function in an inhibitor dose-dependent manner. CONCLUSIONS/SIGNIFICANCE: Liver-targeted gene transfer of a myostatin inhibitor is a valuable tool for preclinical investigation of myostatin blockade and provides novel insights into the long-term effects and shortcomings of myostatin inhibition on striated muscle." 

Now this adeno-associated virus seemed to inhibit myostatin everywhere(everywhere includes bone) so this has more promise. 

Trichostatin A induces follistatin a myostatin inhibitor.  

Inhibition of myostatin promotes myogenic differentiation of rat bone marrow-derived mesenchymal stromal cells. 

"Mesenchymal stromal cells (MSC) have been thought to be attractive candidates for the treatment of Duchenne muscular dystrophy (DMD), but the rate of MSC myogenesis is very low. Thus MSC treatment for DMD is restricted. Myostatin (Mstn), a negative regulator of myogenesis, is known to be responsible for limiting skeletal muscle regeneration. We hypothesized that inhibition of Mstn by using anti-Mstn antibody (Ab) would ameliorate the myogenic differentiation of MSC in vitro and in vivo. Methods MSC were isolated from rat bone marrow. Induced rat MSC (rMSC) were treated with various concentrations of anti-Mstn Ab. The expression of myogenic differentiation antigen (MyoD), myogenin and myosin heavy chain-type alpha (MHC-alpha) were estimated by immunofluorescence analysis and reverse transcription-polymerase chain reaction (RT-PCR). Adipogenic differentiation of rMSC inhibited by anti-Mstn Ab was evaluated by Oil Red O staining. The expression of dystrophin was detected 16 weeks after anti-Mstn Ab injection and rMSC transplantation by immunofluorescence staining, RT-PCR and Western blot. Motor function, serum creatine kinase (CK) and histologic changes were also evaluated. Results Five-azacytidine-mediated myogenic differentiation induced significant endogenous Mstn expression. Anti-Mstn Ab improved the expression of MyoD, myogenin and MHC-alpha and inhibited adipocyte formation. Sixteen weeks after transplantation, the inhibition of Mstn had improved motor function and muscle mass. In accordance with the increased motor function and muscle mass, dystrophin expression had increased. Furthermore, serum CK and centrally nucleated fiber (CNF) levels decreased slightly, suggesting specific pathologic features of the dystrophic muscle were partially restored. Conclusions Using anti-Mstn Ab, we found that inhibition of Mstn improved myogenic differentiation of rMSC in vitro and in vivo. A combination of Mstn blockade and MSC transplantation may provide a pharmacologic and cell-based strategy for the treatment of DMD." 

So there are anti-myostatin antibodies. There is some indication that aerobic exercise may inhibit myostatin... 

Myostatin Decreases with Aerobic Exercise and Associates with Insulin Resistance. 

"There is mounting evidence that skeletal muscle produces and secretes biologically active proteins or "myokines" that facilitate metabolic cross talk between organ systems. The increased expression of myostatin, a secreted anabolic inhibitor of muscle growth and development, has been associated with obesity and insulin resistance. Despite these intriguing findings, there have been few studies linking myostatin and insulin resistance. METHODS.: To explore this relationship in more detail, we quantified myostatin protein in muscle and plasma from 10 insulin-resistant, middle aged (53.1 +/- 5.5 years) men before and after 6 months of moderate aerobic exercise training (1200 kcal/wk at 40-55% peak VO2). To establish a case-effect relationship we also injected C57/Bl6 male mice with high-physiologic levels of recombinant myostatin protein. RESULTS.: Myostatin protein levels were shown to decrease in muscle (37%, P=0.042, n=10) and matching plasma samples (28.7 pre-training to 22.8 ng/ml post-training, P=0.003, n=9) with aerobic exercise. Furthermore, the strong correlation between plasma myostatin levels and insulin sensitivity (R2 = 0.82, P<0.001, n=9) suggested a cause-effect relationship that was subsequently confirmed by inducing insulin resistance in myostatin-injected mice. A modest increase (44%) in plasma myostatin levels was also associated with significant reductions in the insulin-stimulated phosphorylation of AKT (Thr308) in both muscle and liver of myostatin treated animals. CONCLUSIONS.: These findings indicate that both muscle and plasma myostatin protein levels are regulated by aerobic exercise and furthermore, that myostatin is in the causal pathway of acquired insulin resistance with physical inactivity." 

Exercise increases insulin sensitivity.  Is it the increase in insulin sensitivity that inhibits myostatin or something with the exercise itself?  Also, only myostatin in the muscle decreased; we don't know about the bone.  There is also evidence that resistance exercise inhibits myostatin too but does that include the bone or just the muscle..

Growing Taller by inhibiting the myostatin gene?

It is well known in the bodybuilding community that Myostatin is a gene that inhibits muscle mass.  Turns out it has properties on height gain as well.  A mutation in the myostatin receptor and a mutation in Myostatin will have positive effects as well.  There have been a couple of people born without the presence of Myostatin.

Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. 

"Myostatin (GDF-8) is a member of the transforming growth factor-beta (TGF-beta) superfamily that is highly expressed in skeletal muscle, and myostatin loss-of-function leads to doubling of skeletal muscle mass. Myostatin-deficient mice have been used as a model for studying muscle-bone interactions, and here we review the skeletal phenotype associated with altered myostatin signaling. It is now known that myostatin is a key regulator of mesenchymal stem cell proliferation and differentiation[More proof that LSJL works by causing the differentiation of mesenchymal stem cells into chondrocytes], and mice lacking the myostatin gene show decreased body fat and a generalized increase in bone density and strength. The increase in bone density is observed in most anatomical regions, including the limbs, spine, and jaw, and myostatin inhibitors have been observed to significantly increase bone formation. Myostatin is also expressed in the early phases of fracture healing, and myostatin deficiency leads to increased fracture callus size and strength. Together, these data suggest that myostatin has direct effects on the proliferation and differentiation of osteoprogenitor cells, and that myostatin antagonists and inhibitors are likely to enhance both muscle mass and bone strength." 

It doesn't mention that myostatin has an impact on cartilage and chondrocytes but if it has impacts on mesenchymal stem cell proliferation than at the bare minimum it increases the number of MSCs available for chondrogenic differentiation.

"Myostatin circulates in the blood in a latent form bound to a propeptide, which gets cleaved by BMP1/Tolloid matrix metalloproteinase releasing the active form. Follistatin and follistatin–related gene (FLRG) are other proteins that can bind and inhibit the activity of myostatin by maintaining its latency2,5. Active myostatin binds to its receptor, the type IIB activin receptor (ActRIIB), with high affinity and regulates the expression of its target genes through a TGF-β signaling pathway. Recent studies also show that myostatin can activate the p38 MAPK, Erk1/2, and Wnt pathways[possible pathways that can indirectly affect myostatin's inhibition of height growth]" 

So you can also inhibit myostatin by inhibiting BMP1, increasing the levels of follistatin, inhibiting type IIB activin, and by preventing the effects of Myostatin in the pathways it triggers like the MAPK or Wnt signaling pathways.

The scientists speculate that the effect on bone may be due to an indirect effect based on muscle mass but the degree of adaption is just too great for it to be an effect of muscle mass alone.

SNPs in the myostatin gene of the mollusk Chlamys farreri: association with growth traits. 

"Myostatin (MSTN) is a member of the transforming growth factor-beta superfamily which negatively regulates growth of muscle tissue. In this study, 103 cultivated Chlamys farreri individuals were screened for polymorphisms in the MSTN gene using PCR-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods. Two mutations were found: A/G at position 327 in exon 2, which caused an amino acid change from Thr to Ala (Thr305Ala), and C/T at position 289 in exon 3, which caused an amino acid change from Cys to Arg (Cys422Arg). One way ANOVA of the SNPs and growth traits showed that genotype GG of primer M5 had significantly higher body mass, soft-tissue mass, adductor muscle mass, shell length, shell height, absolute growth rate of shell height and body mass than those of genotype AG and AA (P<0.05). Genotype frequencies of genotype AA, AG and GG were 68.94%, 27.18% and 3.88%, respectively. The results present evidence that the C. farreri MSTN gene may be selected as a candidate gene for these growth traits." 

Essentially the mollusks that had Myostatin inhibition(or specific polymorphisms within the Myostatin gene) were taller than those who were able to express Myostatin. 

Myostatin (GDF-8) deficiency increases fracture callus size, Sox-5 expression, and callus bone volume. 

"Myostatin (GDF-8) is a negative regulator of skeletal muscle growth and mice lacking myostatin show increased muscle mass. We have previously shown that myostatin deficiency increases bone strength and biomineralization throughout the skeleton, and others have demonstrated that myostatin is expressed during the earliest phase of fracture repair. In order to determine the role of myostatin in fracture callus morphogenesis, we studied fracture healing in mice lacking myostatin. Adult wild-type mice (+/+), mice heterozygous for the myostatin mutation (+/-), and mice homozygous for the disrupted myostatin sequence (-/-) were included for study at two and four weeks following osteotomy of the fibula. Expression of Sox-5 and BMP-2 were significantly upregulated in the fracture callus of myostatin-deficient (-/-) mice compared to wild-type (+/+) mice at two weeks following osteotomy. Fracture callus size was significantly increased in mice lacking myostatin at both two and four weeks following osteotomy, and total osseous tissue area and callus strength in three-point bending were significantly greater in myostatin -/- mice compared to myostatin +/+ mice at four weeks post-osteotomy. Our data suggest that myostatin functions to regulate fracture callus size by inhibiting the recruitment and proliferation of progenitor cells in the fracture blastema. Myostatin deficiency increases blastema size during the early inflammatory phase of fracture repair, ultimately producing an ossified callus having greater bone volume[bone volume includes height] and greater callus strength. While myostatin is most well known for its effects on muscle development, it is also clear that myostatin plays a significant, direct role in bone formation and regeneration." 

Perhaps if Myostatin was inhibited pre-limb lengthening surgery.  The bone could be stretched by more than one mm a day. 

"The [fracture healing] process can be separated into three general phases: an initial inflammatory phase, a chondrogenic phase, and an osteogenic phase. The inflammatory phase is characterized by increased expression of GDF8[GDF8 is Myostatin], BMP2[BMP-2 helps initial chondrogenic differentiation, however BMP-2 is not enough to induce chondrogenic differentiation], and Wnt-5A, the chondrogenic phase by elevated expression of GDF5[GDF5 enhances extracellular matrix production], TGFβ2,3[TGF-Beta3 Is capable of inducing chondrogenic differentiation], and beta-catenin[Beta-Catenin can be induced by BMP-2 so this is expected], and the osteogenic phase by expression of BMP3,4,7,8, and Frizzled. The role of early GDF8 (myostatin) expression in the callus during the inflammatory phase of fracture healing has, however, been difficult to interpret since this factor is most well known for its effects on myogenesis. It is now known that the receptor for myostatin is expressed in bone-marrow derived stromal cell, and that myostatin can stimulate adipogenic differentiation in mesenchymal stem cells whereas its absence increases osteogenic differentiation. Myostatin regulates myogenic differentiation in part by suppressing the expression of myogenic factors such as MyoD, but it also inhibits myoblast proliferation by increasing levels of p21"


So Myostatin seems to be involved in the stem cell phase rather than at later stages.  So inhibiting myostatin will increase height mainly as a result of increasing stem cell proliferation.  So the earlier myostatin can be inhibited the better.  Probably why Testosterone and Creatine and other Myostatin inhibitors don't increase height that much as much of the stem cells are already differentiated into chondrocytes.


So, inhibiting Myostatin may augment height gain if used in conjunction with methods involving stem cells but after early development Myostatin increases effectiveness as a lot of the stem cells have already differentiated into chondrocytes.

Myostatin may have a direct inhibitory effect on Sox9.  Remember though that you want more Beta-Catenin than Sox9 to maximize height growth.

Myostatin (GDF-8) inhibits chondrogenesis and chondrocyte proliferation in vitro by suppressing Sox-9 expression.

"Here, we investigate a possible direct role for myostatin in chondrogenesis. First, we examined the effects of myostatin on the proliferation of bone marrow stromal cells (BMSCs) and epiphyseal growth plate (EGP) chondrocytes (EGPCs) isolated from myostatin-deficient mice. Results show that myostatin deficiency is associated with a significant (P < 0.001) increase in proliferation of both BMSCs (+25%) and EGPCs (+35%) compared with wild-type cells. Next, we examined the effects of myostatin treatment on chondrogenic differentiation of BMSCs. These experiments show that myostatin treatment starting at either 0 or 48 h induces a significant decrease in collagen type II protein synthesis by 31% (P < 0.001) and 25% (P < 0.05), respectively. Real-time PCR reveals significant (P < 0.01) down regulation of Sox9 mRNA expression with 10 and 100 ng/ml treatments. Together, these findings suggest that myostatin has direct effects on chondrogenesis, and may, therefore, represent a potential therapeutic target for improving bone repair."

So Myostatin directly affects the cells involved in height.