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J Orthop Res. 2004 Jul;22(4):687-96.

Transforming growth factor-beta1 induced alteration of skeletal morphogenesis in vivo.

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  • 1Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Box 665, Rochester, NY 14642, USA.


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 in vivo development model. Addition of Affi-gel agarose beads loaded with TGF-beta1 (10 ng/microl) 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.

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