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

Cristin M. Ferguson, Edward M. Schwarz, J. Edward Puzas, Michael J. Zuscik, Hicham Drissi, Regis J. O'Keefe

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Transforming growth factor beta (TGF-β) 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-β inhibits chondrocyte maturation in cell cultures, the effect of increased TGF-β has not been well characterized in an in vivo development model. Addition of Affi-gel agarose beads loaded with TGF-β1 (10 ng/μl) 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-β1 treated limbs. TGF-β1 also decreased chondrocyte proliferation in the developing anlage. The findings confirm a critical role for TGF-β during skeletal development. A more complete understanding of the role of TGF-β and its down-stream signals will lead to improved understanding and treatment of cartilage diseases.

Original languageEnglish
Pages (from-to)687-696
Number of pages10
JournalJournal of Orthopaedic Research
Volume22
Issue number4
DOIs
StatePublished - 2004

Keywords

  • Chondrocyte biology
  • Chondrocyte maturation
  • Chondrocyte proliferation
  • Embryonic limb development
  • Transforming growth factor-beta

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