11897705

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4

Previous studies in chondrogenic RCJ3.1C5.18 (C5.18) cells showed that growth of these cells at high extracellular Ca(2+) concentrations ([Ca(2+)](o)) reduced the expression of markers of early chondrocyte differentiation. These studies addressed whether raising [Ca(2+)](o) accelerates C5.18 cell differentiation and whether Ca(2+) receptors (CaRs) are involved in coupling changes in [Ca(2+)](o) to cellular responses. We found that high [Ca(2+)](o) increased expression of osteopontin (OP), osteonectin, and osteocalcin, all markers of terminal differentiation, in C5.18 cells and increased the production of matrix mineral. Overexpression of wild-type CaR cDNA in C5.18 cells suppressed proteoglycan synthesis and aggrecan RNA, two early differentiation markers, and increased OP expression. The sensitivity of these parameters to changes in [Ca(2+)](o) was significantly increased, as indicated by left-shifted dose-responses. In contrast, stable expression of a signaling-defective CaR mutant (Phe707Trp CaR) in C5.18 cells, presumably through dominant-negative inhibition of endogenous CaRs, blocked the suppression of aggrecan RNA levels and proteoglycan accumulation and the enhancement of OP expression by high [Ca(2+)](o). These data support a role for CaRs in mediating high [Ca(2+)](o)-induced differentiation of C5.18 cells.

eng

AIM

MEDLINE

0013-7227

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NLM

1467-74

pubmed-meshheading:11897705-Adenoviridae, pubmed-meshheading:11897705-Aggrecans, pubmed-meshheading:11897705-Animals, pubmed-meshheading:11897705-Blotting, Northern, pubmed-meshheading:11897705-Calcification, Physiologic, pubmed-meshheading:11897705-Calcium, pubmed-meshheading:11897705-Cartilage, pubmed-meshheading:11897705-Cell Differentiation, pubmed-meshheading:11897705-Cell Line, pubmed-meshheading:11897705-Chondrocytes, pubmed-meshheading:11897705-Chondroitin, pubmed-meshheading:11897705-Coloring Agents, pubmed-meshheading:11897705-Extracellular Matrix, pubmed-meshheading:11897705-Extracellular Matrix Proteins, pubmed-meshheading:11897705-Immunoblotting, pubmed-meshheading:11897705-Lectins, C-Type, pubmed-meshheading:11897705-Osteopontin, pubmed-meshheading:11897705-Proteoglycans, pubmed-meshheading:11897705-RNA, Messenger, pubmed-meshheading:11897705-Rats, pubmed-meshheading:11897705-Receptors, Calcium-Sensing, pubmed-meshheading:11897705-Receptors, Cell Surface, pubmed-meshheading:11897705-Sialoglycoproteins, pubmed-meshheading:11897705-Transfection

Extracellular Ca(2+)-sensing receptors modulate matrix production and mineralization in chondrogenic RCJ3.1C5.18 cells.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't