INVOLVEMENT OF CELLULAR-METABOLISM OF CALCIUM AND PHOSPHATE IN CALCIFICATION OF AVIAN GROWTH PLATE CARTILAGE

Past work established that matrix vesicles (MV) are primary initiators of extracellular mineral deposition in endochondral calcification. Reviewed here are studies on how direct cellular metabolism of Ca2+ and inorganic phosphate (P(i), and cellular interaction with the matrix, are involved in the formation of calcifiable MV. Presented is a working model of how chondrocytes in growth plate (GP) cartilage are envisioned to induce the formation of calcifiable MV. In part, this model is based on recent laser confocal imaging of living cartilage tissue sections with Indo-I AM, a fluorescent permeant Ca2+ probe. These studies indicate that GP chondrocytes actively acquire Ca2+, concentrate it to the cell periphery and exfoliate it as Ca2+-rich MV. Data from direct chemical analysis and P-31-NMR studies on freshly isolated cells show that GP chondrocytes are depleted of ATP and have elevated cytosolic P(i), a condition prerequisite to formation of Ca2+-acidic phospholipid (APL)-P(i) complex-primed MV. Chondrocyte cell membrane processes from which MV arise have been found to be tightly linked to the cartilage-specific extracellular matrix collagens and proteoglycans. Annexins V and VI, APL-dependent Ca2+-binding proteins that form Ca2+ channels in chondrocytes and MV membranes, also bind to the matrix collagens and may serve as mechano-transducers in GP cartilage, gating Ca2+ entrance into the cells and MV. This interaction between the extracellular matrix and chondrocytes appears to facilitate Ca2+ loading of chondrocytes, formation of Ca2+ and P(i)-primed MV and rapid induction of mineralization in GP cartilage.