Effects of Interleukin-1 on Syntheses of Alkaline Phosphatase, Type X Collagen, and 1,25-Dihydroxyvitamin D3 Receptor, and Matrix Calcification in Rabbit Chondrocyte Cultures

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Abstract

The effect of IL-1 on expression of the mineralization-related phenotype by chondrocytes was examined. In cultures of rabbit growth plate chondrocytes, IL-1 beta at 0.1 ng/ml caused 95% decreases in alkaline phosphatase activity, alkaline phosphatase mRNA levels, the incorporation of Calcium-45 into insoluble material, and the calcium content during the hypertrophic stage. These effects of IL-1 beta were dose-dependent and were observed in 24-48 h. Furthermore, IL-1 beta suppressed increase in cell size and the syntheses of 1,25-dihydroxyvitamin D3 receptor and type X collagen, other markers of hypertrophy, but had little effect on the synthesis of total protein including type II collagen. The inhibition of calcification was observed only when chondrocytes were exposed to IL-1 before the onset of calcification: IL-1 treatment from the mineralization stage had a marginal effect on Calcium-45 incorporation into insoluble material. These results suggest that IL-1 inhibits chondrocyte hypertrophy and the onset of calcification in ossifying cartilage. (J. Clin. Invest. 1993. 92:2323-2330.) Key words: mineralization. cartilage. cytokine. ossification. fracture

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