Gain Stature with Latency Associated Peptide?

An overgrowth disorder caused by TGF-Beta1 was only present when the gene coding for Latency Associated Peptide was modified and not TGF-Beta upregulation.  LSJL upregulates TGF-Beta (predicted but no change is observed in the gene expression data aside from a decrease in TGFbR1) but does it increase LAP too?

The single-molecule mechanics of the latent TGF-β1 complex.

"Together with its latency-associated peptide (LAP), TGF-β1 binds to the latent TGF-β1-binding protein-1 (LTBP-1), which is part of the extracellular matrix (ECM). Transmission of cell force via integrins is one major mechanism to activate latent TGF-β1 from ECM stores[LSJL can cause cell force]. Latent TGF-β1 mechanical activation is more efficient with higher cell forces and ECM stiffening.
We analyzed how forces exerted on the LAP lead to conformational changes in the latent complex that can ultimately result in TGF-β1 release. We demonstrate the unfolding of two LAP key domains for mechanical TGF-β1 activation: the α1 helix and the latency lasso, which together have been referred to as the "straitjacket" that keeps TGF-β1 associated with LAP. The simultaneous unfolding of both domains, leading to full opening of the straitjacket at a force of ~40 pN[a pico neuton which is 1 X10(-12) of a Newton so the amount of force in LSJL shouldn't be a problem], was achieved only when TGF-β1 was bound to the LTBP-1 in the ECM.
Our results directly demonstrate opening of the TGF-β1 straitjacket by application of mechanical force in the order of magnitude of what can be transmitted by single integrins. For this mechanism to be in place, binding of latent TGF-β1 to LTBP-1 is mandatory[does this occur in adult epiphyseal bone marrow]. Interfering with mechanical activation of latent TGF-β1 by reducing integrin affinity, cell contractility, and binding of latent TGF-β1 to the ECM provides new possibilities to therapeutically modulate TGF-β1 actions."

"Integrins activate latent TGF-β1 by at least two different mechanisms. One depends on proteases, which seem to be guided to the LLC[large latent complex which is composed of LAP and LTBP-1] by associating with integrins. The other is independent of proteolysis and involves transmission of cell traction forces to the LAP moiety of LLC"

"Whereas the overall LAP structure is predicted to be mechanically stable, two stretches in the molecule are prone to unfolding: the α1 helix and the latency lasso loop. Together both domains form a configuration that traps TGF-β1 in the SLC like a “straitjacket”"

The question is now does TGF-Beta form the complex with LAP and LTBP-1 in adult epiphyseal bone marrow?

According to this study TGF-Beta would be activated in LSJL(MMP-3 is the most significant gene upregulated by LSJL upregulated almost 5-fold):

The first stage of transforming growth factor beta1 activation is release of the large latent complex from the extracellular matrix of growth plate chondrocytes by matrix vesicle stromelysin-1 (MMP-3).

"Transforming growth factor beta-1 (TGF-beta1) is secreted in a biologically inactive form and stored in the extracellular matrix as a 290 kDa complex consisting of the mature TGF-beta1 homodimer (Mr 25 kDa), the latency-associated peptide (LAP; Mr 75 kDa), and the latent TGF-beta1 binding protein-1 (LTBP1; Mr 190 kDa). Latent TGF-beta1, composed of these three components, is known as the "large latent TGF-beta1 complex." In contrast, latent TGF-beta1 without LTBP1 is known as "small latent TGF-beta1." For all latent forms, dissociation of the TGF-beta1 homodimer from LAP is necessary for growth factor activation and acquisition of biological activity. Matrix vesicles produced by growth plate chondrocytes contain matrix metalloproteinases that can activate small latent TGF-beta1. The enzyme responsible for this is matrix metalloproteinase-3 (MMP-3), although matrix vesicles also contain MMP-2 and plasminogen activator. The present study tested the hypothesis that matrix vesicle enzymes are also involved in the release of the large latent TGF-beta1 complex stored in the extracellular matrix. Matrix vesicles were isolated from cultures of resting zone and growth zone chondrocytes and metalloproteinases present in the matrix vesicles extracted with guanidine-HCl. Chondrocyte extracellular matrices were prepared by lysing confluent cultures and removing the lysed cells. The matrices were incubated with matrix vesicle extracts and the release of total and active TGF-beta1 was determined. To determine if MMP-2 or MMP-3 was involved in the release, matrix vesicle extracts were preincubated with anti-MMP-2 antibody or anti-MMP-3 antibody to selectively deplete the enzyme activity. Matrices were also treated with rhMMP-2 or rhMMP-3. To determine the identity of the released protein(s), digests were separated on SDS-polyacrylamide gels and Western blotting analysis was performed using a specific antibody to LTBP1. Matrix vesicle extracts released both active and total (=latent + active) TGF-beta1 in a time-dependent manner, with peak release after 1 hour of incubation. The amount of total TGF-beta1 released was 10 times higher than the release of active TGF-beta1. The effect of the matrix vesicle extracts was dose-dependent; in addition, the amount and ratio of active to total TGF-b1 released was very similar, irrespective of the source of matrix or matrix vesicle extracts. Pre-incubation of matrix vesicle extracts with anti-MMP-3 antibody blocked the release of active and total TGF-beta1, whereas pre-incubation with pre-immune IgG or anti-MMP-2 antibody had no effect. The addition of rhMMP-3, but not rhMMP-2, caused a dose-dependent increase in the release of total, but not active, TGF-beta1. Both matrix vesicle extracts and rhMMP-3 released the large latent TGF-beta1 complex from the matrix. In addition to the expected 290, 230, and 190 kDa bands, samples run without reduction also contained proteins of molecular weights 110 and 50 kDa that reacted with the anti-LTBP1 antibody. When these same samples were electrophoresed after reduction, the high molecular weight immunoreactive bands disappeared and three bands of molecular weight 75, 32, and 25 kDa were observed. These results indicate that matrix vesicles contain enzymes, especially MMP-3, which are responsible for the release of TGF-beta1 from the matrix, most of which is in latent form. Further, the data suggest that release of the large complex occurs via cleavage at several novel sites in the 130 kDa LTBP1 molecule. Since matrix vesicle MMP-3 is also able to activate small latent TGF-beta1, these results suggest that the large latent TGF-beta1 complex protects against activation of the small latent TGF-beta1. release of the large latent TGF-bl complex from the matrix and activation of the latent growth factor are only two steps of what must be at least a three-step process[we need to make sure LSJL follows all three steps]."

Specificity of latent TGF-ß binding protein (LTBP) incorporation into matrix: role of fibrillins and fibronectin. states that LTBP-1 association depends on the fibronectin network.

Fibronectin is required for integrin alphavbeta6-mediated activation of latent TGF-beta complexes containing LTBP-1. identifies integrin alphavbeta6 as the key for activating latent TGF-Beta.  LSJL upregulates Integrin Alpha V which could lead to higher levels of integrin alphavebeta6.

Thus, intregin alphavbeta6, MMP-3, LAP, and LTBP-1 are all proteins to look for as possibly helping increase height by increasing active TGF-Beta levels.