Effects of various growth factors on a chondrocyte differentiation model.

We developed a new 4-dimensional differentiation model of growth-cartilage cells (temporally and spatially regulated). composed of a high-density suspension culture of rabbit costal chondrocytes. In this system, fibroblast growth factor (FGF) or transforming growth factor-beta (TGF beta) stimulated proliferation and matrix synthesis, but reversibly inhibited terminal differentiation-induction of alkaline phosphatase (Alpase) activity, type X collagen synthesis and subsequent calcification. When parathyroid hormone (PTH) was added to the differentiation model, both the induction of Alpase and calcium uptake were reversibly suppressed. In contrast, calcitonin (CT) stimulated Alpase activity and calcium uptake dose-dependently. Bone morphogenetic protein (BMP) strongly stimulated DNA synthesis of chondrocytes in the presence of FGF and induced rapid maturation of chondrocytes at a growing stage. Moreover, BMP stimulated Alpase activity in multilayered chondrocytes at the calcifying stage.