Transforming growth factor-β1 induced alteration of skeletal morphogenesis in vivo

Transforming growth factor beta (TGF-beta) is expressed in the growth plate and is an important regulator of chondrocyte maturation. Loss of function results in premature chondrocyte maturation both in vitro and in vivo. While TGF-beta inhibits chondrocyte maturation in cell cultures, the effect of increased TGF-beta has not been well characterized in an ill vivo development model. Addition of Affi-gel agarose beads loaded with TGF-beta1 (10 ng/mul) to developing stage 24-25 chick limb buds resulted in limb shortening and altered morphology. In situ hybridization studies showed down regulation of Indian hedgehog (ihh), bone morphogenetic protein 6 (bmp6), and collagen type X (colX) expression, markers of chondrocyte maturation, in TGF-beta1 treated limbs. TGF-beta1 also decreased chondrocyte proliferation in the developing anlage. The findings confirm a critical role for TGF-beta during skeletal development. A more complete understanding of the role of TGF-beta and its down-stream signals will lead to improved understanding and treatment of cartilage diseases. (C) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.