Monday, October 10, 2011

MEPE in height growth

MEPE is a novel regulator of growth plate cartilage mineralization

"Matrix extracellular phosphoglycoprotein (MEPE) belongs to the SIBLING protein family which play key roles in biomineralization. The growth plates of MEPE-overexpressing mice display severe morphological disruption, . MEPE and its cleavage product, the acidic serine aspartate-rich MEPE-associated motif (ASARM) peptide,  [are] localised to the hypertrophic zone of the growth plate. The phosphorylated (p)ASARM peptide inhibits ATDC5 chondrocyte matrix mineralization. Stable MEPE-overexpressing ATDC5 cells also had significantly reduced matrix mineralization in comparison to the control cells. The addition of the non-phosphorylated (np)ASARM peptide promoted mineralization in the ATDC5 cells. The peptides and the overexpression of MEPE did not affect the differentiation of the ATDC5 cells. We utilized the metatarsal organ culture model. pASARM peptide [inhibits] mineralization at two stages of development. Like in the ATDC5 cells, the peptides did not affect the differentiation of the metatarsals indicating that the effects seen on mineralization are direct, as is additionally confirmed by no change in alkaline phosphatase activity or mRNA expression. In the metatarsal organ cultures, the pASARM peptide also reduced endothelial cell markers and vascular endothelial growth factor mRNA expression. MEPE [is] an important regulator of growth plate chondrocyte matrix mineralization through its cleavage to an ASARM peptide."

"Mineralization is a biphasic process which is under tight control so as to ensure levels of calcium (Ca2 +) and inorganic phosphate (Pi) are permissive for effective HA[hydroxyapitate crystals] formation"

"The expression of MEPE is increased during osteoblast matrix mineralization"<-overexpression of MEPE less mineralization and null MEPE equals more mineralization.

"Mepe was expressed abundantly by growth plate chondrocytes[especially hypertrophic chondrocytes]" This expression is dependent on cleavage and phosphorylation of Mepe.

"ASARM peptide is cleaved from MEPE by cathepsin B"

"ALP, NPP1 and ANK are all central regulators of levels of PPi, a mineralization inhibitor, and thus the deposition of HA"

"ASARM peptide to inhibit matrix mineralization in in vitro osteoblast cultures" Phosphorylation of ASARM(pASARM) is essential for this inhibition. pASARM decreased Col2A1 expression

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