Expression of GABA(A) and GABA(B) receptors in rat growth plate chondrocytes: activation of the GABA receptors promotes proliferation of mouse chondrogenic ATDC5 cells.
"local production of gamma-aminobutyrate (GABA) [occurs] in hypertrophic-zone chondrocytes of the rat tibial growth plate. Chondrocytes expressed both GABA(A) and GABA(B) receptor subunit mRNAs as well as the corresponding proteins necessary for the assembly of functional receptors. The GABA(A) receptor subunits detected included alpha1-alpha4, alpha6, beta1-beta3, and delta, and both R1 and R2 subunits of GABA(B) receptors were detected. All receptor subunits were expressed in chondrocytes of the proliferative and hypertrophic zones. GABA is an autocrine/paracrine factor that regulates the physiological state of the growth plate. The mouse chondrogenic cell line ATDC5 showed the presence of mRNAs and the corresponding proteins for GABA(A) receptor alpha1, beta2, and beta3 subunits and GABA(B) receptor R1 and R2 subunits. GABA, muscimol (a GABA(A) receptor agonist), and baclofen (a GABA(B) receptor agonist) increased 5-bromodeoxyuridine (BrdU) incorporation into ATDC5 cells. The effect of muscimol was blocked by bicuculline (a GABA(A) receptor antagonist), and the effect of baclofen was blocked by CGP 35348 (a GABA(B) receptor antagonist). GABA contributes to ATDC5 cell proliferation via GABA(A) and GABA(B) receptors and these mechanisms may be involved in cartilaginous cell growth."
So GABA contributes to growth rate but does it help increase adult height? And it should be noted that it was stimulation of the receptors that increased growth rate so it's unclear what effect GABA supplementation would have. The GABA was produced by the growth plate chondrocytes themselves after all.
"GABAB receptors are coupled to G proteins, and activation of these receptors provokes diverse cellular and biochemical responses by modulation of adenylyl cyclase activity or of Ca2+ or K+ channels"<-Forskolin is an adenylyl cyclase activator. Forskolin is pro-chondrogenic. Maybe adenylyl cyclase is pro chondrogenic as well. Calcium channels help with height increase as well. If GabaB exerts these affects on all cells which would include MSCs then GABAb would help increase height.
GABA is most associated with neuronal cellular differentiation however.
Here's a study that shows the effect of GABA on Ca2+ sensing receptors the effect on MSCs might be the same as on chondrocytes.
"Extracellular calcium-sensing receptors (CaRs) and metabotropic or type B gamma-aminobutyric acid receptors (GABA-B-Rs), two closely related members of family C of the G protein-coupled receptor superfamily, dimerize in the formation of signaling and membrane-anchored receptor complexes. CaRs and two GABA-B-R subunits (R1 and R2) are expressed in mouse growth plate chondrocytes (GPCs). Interactions between these receptors influence the expression and function of the CaR and extracellular Ca(2+)-mediated cell differentiation. Both CaRs and the GABA-B-R1 and -R2 were expressed in the same zones of the growth plate and extensively colocalized in intracellular compartments and on the membranes of cultured GPCs. The GABA-B-R1 co-immunoprecipitated with the CaR, confirming a physical interaction between the two receptors in GPCs. In vitro knockout of GABA-B-R1 genes, using a Cre-lox recombination strategy, blunted the ability of high extracellular Ca(2+) concentration to activate phospholipase C[PLC] and ERK1/2, suppressed cell proliferation, and enhanced apoptosis in cultured GPCs. In GPCs, in which the GABA-B-R1 was acutely knocked down, there was reduced expression of early chondrocyte markers, aggrecan and type II collagen, and increased expression of the late differentiation markers, type X collagen and osteopontin[So GABA-B-R1 upregulation may increase expression of early chondrocyte markers]. Physical interactions between CaRs and GABA-B-R1s modulate the growth and differentiation of GPCs, potentially by altering the function of CaRs."
"High extracellular Ca2+ concentration ([Ca2+]e) activates G protein-coupled signaling pathways and alters matrix synthesis, mineralization, and gene expression in GPCs, all in directions indicative of terminal differentiation"<-But that high extracellular Ca2+ concentration may also induce chondrogenic differentiation of MSCs.
"GABA-B-Rs [may] modulate the processing and trafficking of CaRs endogenously and, therefore, the availability of the CaRs on the cell surface to signal to the cell’s interior. Direct interactions between GABA-B-Rs and CaRs [may] produce protein complexes that have distinct Ca2+-binding properties and specialized abilities to activate downstream signaling pathways. Our signaling assays support the latter scenario, blocking the GABA-B-R1 expression in GPCs reduced cellular sensitivity of extracellular Ca2+ to activate ERK1/2 without affecting the maximal level of ERK1/2 phosphorylation."
"blocking GABA-B-R1 expression also suppressed high [Ca2+]e-induced activation of PLC in GPCs. Endogenous GABA-B-R1s may have a role to enhance CaR-mediated signaling in these cells."
LSJL alteration of PLC expression was predicted.
It is possible that GABA may help induce chondrogenic differentiation of MSCs via Ca2+ channels. GABA may be produced endogenously by chondrocytes but it's unclear whether it's produced by MSCs. If MSCs have receptors for GABA but don't produce GABA themselves than exogenous GABA may definitely help increase height. However, most of the benefits of GABA were obtained by increasing GABA receptors and not GABA itself as chondrocytes already produce GABA.
I have a serious question to ask you. LSJL does not work foe everyone. Someone in minigolfer's forum claim no gain results. And someone said LSJL That is bad for growth and will in fact accelerated growth plates ossification. This explains because at a certain point it's no longer work... It's true?
ReplyDeleteEndogenously produced adenosine regulates articular cartilage matrix homeostasis: enzymatic depletion of adenosine stimulates matrix degradation.
ReplyDelete--
it seems theres alot of things that happen at night to maintain growth, possibly alot of mysterious local factors