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• W2079873471 abstract "Abstract Zinc (Zn 2+ ) has long been known to play important roles in mineralization and ossification of skeletal tissues, but the mechanisms of Zn 2+ action are not well understood. In this study we investigated the effects of Zn 2+ on mineralization in a cell culture system in which terminal differentiation and mineralization of hypertrophic growth plate chondrocytes was induced by retinoic acid (RA) treatment. Addition of Zn 2+ to RA‐treated cultures decreased mineralization in a dose‐dependent manner without affecting alkaline phosphatase (APase) activity. Characterization of matrix vesicles (MVs), particles that initiate the mineralization process, revealed that vesicles isolated from RA‐treated and RA/Zn 2+ ‐treated cultures showed similar APase activity, but vesicles from RA/Zn 2+ ‐treated cultures contained significantly less Ca 2+ and Pi. MVs isolated from RA‐treated cultures were able to take up Ca 2+ and mineralize in vitro, whereas vesicles isolated from RA/Zn 2+ ‐treated cultures were not able to do so. Detergent treatment, which ruptures the MV membrane and exposes preformed intravesicular Ca 2+ ‐Pi‐phospholipid complexes, did not restore the Ca 2+ uptake abilities of MVs isolated from RA/Zn 2+ ‐treated cultures, suggesting that vesicles from RA/Zn 2+ ‐treated cultures did not contain functional Ca 2+ ‐P i − phospholipid complexes. Zn 2+ treatment did not affect the content of annexins II, V, and VI in MVs or the Ca 2+ ‐dependent, EDTA‐reversible binding of these molecules to the membrane surface. However, Zn 2+ treatment did affect the EDTA‐nonreversible binding of these molecules to the MV membrane, suggesting that Zn 2+ interferes with the assembly of annexins in the MV membrane. In addition, Zn 2+ inhibited annexin II‐, V‐, and VI‐mediated Ca 2+ influx into liposomes. In conclusion, Zn 2+ inhibits the mineralizing competence of intravesicular Ca 2+ ‐P i –phospholipid complexes and function of annexin channels, thereby controlling Ca 2+ influx into MVs, the formation of the first crystal phase inside the vesicles and initiation of mineralization. (J Bone Miner Res 2000;15:261–270)" @default.
• W2079873471 created "2016-06-24" @default.
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• W2079873471 date "2000-02-01" @default.
• W2079873471 modified "2023-10-17" @default.
• W2079873471 title "Regulatory Roles of Zinc in Matrix Vesicle-Mediated Mineralization of Growth Plate Cartilage" @default.
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• W2079873471 doi "https://doi.org/10.1359/jbmr.2000.15.2.261" @default.
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