Contractile forces generated by articular chondrocytes in collagen-glycosaminoglycan matrices.
"The objective of the study was to directly measure the force of contraction of adult articular chondrocytes and to examine their contractile behavior in collagen-glycosaminoglycan analogs of extracellular matrix[this is for articular rather than growth plate cartilage but force generation and contractile behavior should be similar between articular carilage and growth plate cartilage]. The contractile forces generated by passages 2 and 3 adult canine articular chondrocytes were measured using a cell force monitor. Passage 2 cells seeded in a collagen-glycosaminoglycan scaffold were capable of generating a force of 0.3 nN/cell. Chondrocytes subcultured through a third passage generated a force twice that level, paralleling the increase in the alpha-smoothmuscle actin (SMA) content of the cells. Treatment of passage 3 cells with staurosporine reduced the force of contraction by approximately one-half, reflecting the effects of this agent in reducing the SMA content of the cells and disrupting the microfilaments. These values compare with 1 nN previously reported for lapine dermal fibroblasts of passage 5-7[dermal fibroblasts are a type of skin cell that are capable of stretching and elongating], using the same apparatus. Direct live cell imaging documented the contractile behavior of the articular chondrocytes in the collagen-glycosaminoglycan matrix in the time frame in which the force was directly measured in the cell force monitor. the cells acted individually and in unison to buckle the collagen struts[so the chondrocytes could act in unison in the growth plate to make bone longer] making up the matrix. Adult articular chondrocytes are capable of generating a SMA-enabled force of contraction sufficient to model extracellular matrix molecules."
BMP-2 causing Smad 1/5/8 phosphorylation was found to accelerate mineralization and terminal differentiation whereas TGF-Beta1 causing Smad 2/3 phosphorylation was found to deccelerate terminal differentiation. Whether either gene inactivation can increase height is unknown. ESL-1 inhibits TGF-Beta and when ESL-1 knockout mice were generated height decrease resulted. So when TGF-Beta1 can't be inhibited height increase results.
According to the study "Bone Morphogenetic Protein-2-Induced Signaling and Osteogenesis Is Regulated by Cell Shape, RhoA/ROCK, and Cytoskeletal Tension", "BMP triggered rapid and sustained RhoA/Rho-associated protein kinase (ROCK) activity and contractile tension only in spread cells". Now chondrocyte growth plate cells tend not to be spread whereas osteoblast cells tend to be spread. So this indicates possibly that BMP doesn't generate contractile force in unspread cells(like chondrocytes). "BMP-induced osteogenesis is progressively antagonized with decreased cell spreading". So BMP is more likely to induce chondrogenesis when the cells are closer perhaps this is linked to the contractile forces.
So it's still unclear which is better for height growth TGF-Beta1 and BMP-2. LSJL upregulates TGF-Beta1 and BMP-2. If BMP-2 can't induce contractile forces in unspread cells then that may be a reason why TGF-Beta1 and BMP-2 would have different effects on adult height. If BMP-2 does increase adult height more than TGF-Beta1 then that would be an indication that chondrocyte cell forces are not the driving force behind bone lengthening. BMP-2 driven chondrocytes being less able to generate contractile forces than TGF-Beta1 chondrocytes might result in less efficiently being able to model the matrix thus more time to proliferate before hypertrophy. BMP-2 chondrocytes have less type X collagen(hyptrophic collagen) and more Type II collagen. Since BMP-2 chondrocytes can't generate any force from chondrocyte hypertrophy they have to generate it all by mitotic cell rounding thus resulting in more chondrocyte proliferation.
So, contractile forces may still be the force behind bone lengthening but with BMP-2 chondrocytes it's primarily chondrocyte proliferation driven whereas with TGF-Beta1 chondrocytes it's chondrocyte proliferation driven.
LSJL alteration of either Smurf1 or 2 is predicted and downregulates Smad1.
"Smad ubiquitin regulatory factor 1 (Smurf1) and Smurf2 induce the ubiquitination and degradation of Smad1 and Smad5"<-We need to know the proportion of how much LSJL upregulates Smad1 relative to the Smurf's.
"Smurf1 and Smurf2 interact with nuclear Smad7 and induce the nuclear export of Smad7. Smurf–Smad7 complexes then associate with type I receptor for TGF-β and enhance its turnover "<-LSJL had no effect on Smad7 but LSJL did upregulate TGF-Beta Receptor I.
"Smurf1 binds to BMP type I receptors via Smad6 and Smad7, and that it induces the ubiquitination and degradation of these receptors. Thus, Smad6 and Smurf1 cooperatively down-regulate BMP signals by degradation of R-Smads as well as BMP receptors."<-LSJL induces BMP RII rather than BMP RI which is consistent with the elevated Smurf levels.
"Exogenous rhBMP2 added to Smurf1 transgenic cartilage in organ cultures of metatarsal rudiments at 15.0 d.p.c. caused proliferative cartilage outgrowth and hypertrophic center formation as in normal mice. "<-So maybe the Smurf1 upregulation doesn't inhibit the height growth inducing elements of LSJL.
So BMP-2 may be better for height growth than TGF-Beta1 and this may be linked to BMP-2 chondrocytes lower contractile ability which results in slower terminal differentiation and mineralization.
Great information as always!
ReplyDeleteNot sure why you don't post on the LSJL forums anymore but this type of information should really be flowing out there and discussed!
Quick question though about risks of LSJL.
What are the differences between the bones in the legs and the bones in the arms other than size?
What I mean specifically is, it is suggested to clamp the ankles but I would have to think that if you were to do this to your wrists you would get carpal tunnel?
Can carpal tunnel happen in the ankles? Or anything similar to it?
carpal tunnel is b/c of nerve compression specifically of the median nerve. When you clamp your lateral and medial malleolus in your ankle, you are clamping the bone only. The nerves lie either medial or lateral to the malleolus(the bump). As long as you avoid the nerves you will be fine. You would know too if you hit the nerve.
ReplyDeleteso osthol has some potential here for contractile force since it increases BMP-2
ReplyDeleteWould pSarm be a recommended supplement to take then since it has osthol in it?
DeleteAmount Per Serving
pSarm 50mg
Osthol 90%
Natural PhytoAndrogens 220mg
Hibiscus Rosa-Sinensis
Zingiberis Officinale
Eurycoma Longifolia
Metabolism Complex 180mg
Stinging Nettle Root (Standardized)
Ellagic Acid Standardized (40% From Red Raspberry)
Quercetin
Piperine
Yohimbe (Standardized For Yohimbine)
http://www.illpumpyouup.com/legal-gear/methyl-1-d-psarm.htm