Friday, March 12, 2010


Vanin-1 pantetheinase drives increased chondrogenic potential of mesenchymal precursors in ank/ank mice.

"Widespread endochondral and intramembranous ectopic bone formation is mediated by extracellular PP(i) deficiency that develops in ank/ank mice. Herein we report on the rapid condensation into chondrogenic nodules of cultured ank/ank bone marrow stromal cells (BMSCs). We compared the roles of increased chondrogenic potential versus altered osteoblast function in the ank/ank phenotype. To do so, we crossbred ank/ank mice with mice lacking Vanin-1 pantetheinase, which inhibits synthesis of the chondrogenesis regulator glutathione, since we observed increased Vanin-1 expression and pantetheinase activity and decreased glutathione in ank/ank BMSCs. Vnn1(-/-) BMSCs demonstrated delayed chondrogenesis mediated by increased glutathione. Moreover, increased chondrogenesis of ank/ank BMSCs and increased chondrogenic transdifferentiation and calcification by ank/ank aortic smooth muscle cells and explants were corrected by Vanin-1 knockout. Osteoblastogenesis was accelerated in ank/ank mesenchymal stem cells. However, in cultured ank/ank osteoblasts, Vanin-1 knockout actually increased specific alkaline phosphatase activity and lowered extracellular PP(i), and did not correct increased calcification. Moreover, Vanin-1 knockout failed to correct the ank/ank skeletal soft tissue phenotype. Therefore, ank/ank periskeletal soft tissue calcification appears more dependent on altered osteoblastic function than enhanced chondrogenic potential and is not dependent on Vanin-1; however, Vanin-1 regulates chondrogenesis via glutathione metabolism and is critical for accelerated chondrogenesis of ank/ank mesenchymal precursors and P(i) donor-driven chondrogenic transdifferentiation and calcification of aortic smooth muscle cells."

"[In] the murine ank mutant of the multiple-pass transmembrane protein ANK [the] PPi transport function is disabled by a spontaneous ANK C-terminal truncation"

"The ank/ank mice, which are markedly depleted in extracellular PPi, do not exhibit any developmental or gross skeletal abnormality at time of birth, but go on to spontaneously develop pathological soft tissue calcification by 2 months of age"

"Functionally significant effects of ANK and extracellular PPi on differentiation in chondrocytes include promotion of chondrocyte maturation and terminal differentiation and regulation of expression of matrix metalloproteinase-13, tissue-nonspecific alkaline phosphatase, and osteocalcin. Moreover, increased chondrogenic transdifferentiation of cultured aortic smooth muscle cells (SMCs) and intra-arterial chondroid metaplasia occur in association with aortic calcification in both ank/ank and NPP1−/− mice."

"Chondrogenesis is modulated by the metabolism of glutathione (GSH), a redox stress regulator that is the major reduced intracellular thiol."

"we directly tested for a role in enhancing MSC chondrogenic potential of the Vanin-1 enzymatic product cysteamine, which suppresses GSH synthesis. Cysteamine (100 nmol/L and, more potently, 1 μmol/L) increased [35S]sulfur incorporation into proteoglycans in wild-type MSCs in pellet culture. Furthermore, cysteamine (1 μmol/L) increased type II collagen expression in wild-type MSCs to levels comparable to those seen in untreated ank/ank MSCs in pellet culture"

There are cysteamine supplements but only by prescription.  It's called Cystagon and it may only accelerate height growth and not increase adult height.

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