Identification of Hormones and Growth Factors Involved in Cartilage Calcification

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We attempted to identify hormones and growth factors that might be involved in the control of cartilage calcification, using rabbit growth plate chondrocytes in centrifuge tubes or on type II collagen gels. In addition, changes in expressions of receptors for various hormones and growth factors prior to the mineralization of cartilage matrix were examined. A factor that inhibited calcification was found to be present in cartilage extracts, and this factor has been partially purified by ultrafiltration and heparin-affinity chromatography. We also found that concanavalin A stimulates both cartilage-matrix synthesis (J. Biol. Chem. 1990) and calcification. The level of receptors for basic fibroblast growth factor was the highest in the proliferative stage of chondrocytes in culture, and decreased to a very low level in the mineralization stage (J. Biol. Chem. 1991). In contrast, the receptor for 1,25(OH)_2-vitamin D increased during the mineralization stage. The levels of receptors for parathyroid hormone and insulin-like growth factor-I were the highest in the matrix-forming stage. The levels of receptors for epidermal growth factor and transforming growth factor beta were constant throughout all stages of chondrocyte cytodifferentiation. These results suggest that different patterns of changes in hormone and growth factor receptors are essential for the onset of terminal differentiation of chondrocytes and calcification.