Transforming growth factor‐beta modulates the expression of osteoblast and chondroblast phenotypes in vitro

Abstract

Transforming growth factor β (TGF-β) has been shown to induce chondrogenesis by embryonic rat mesenchymal cells (Seyedin et al., J. Biol. Chem., 261:5693, 1986). Here we report the effects of bovine TGF-β on the phenotypic expression of differentiated primary rat osteoblastic and chondroblastic cells. Culture of rat calvarial osteoblasts with TGF-β resulted in a dose and time-dependent decrease in alkaline phosphatase activity. Levels of alkaline phosphatase were reduced to less than 10% of control values by 0.4 nM TGF-β. The decrease became apparent after 24 hours and reached a maximum by 72 hours. Similarly, treatment of chondroblasts with 0.4 nM TGF-β resulted in decreased production of cartilage-specific macromolecules: type II collagen and cartilage proteoglycan. Both cell types exhibited dramatic changes in cell shape after treatment with TGF-β. Modulation of these differentiated markers by TGF-β could be mimicked, in part, by addition of fibronectin. Addition of dihydrocytochalasin B blocked the inhibition of phenotypic expression by TGF-β. These results indicate that TGF-β inhibits phenotypic expression by osteoblasts and chondroblasts in vitro and suggest that this activity of TGF-β may be mediated through interactions between the extracellular matrix and cytoskeletal elements.