Transforming growth factor-beta1 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 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.
Ferguson
Cristin M
CM
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Box 665, Rochester, NY 14642, USA.
Schwarz
Edward M
EM
Puzas
J Edward
JE
Zuscik
Michael J
MJ
Drissi
Hicham
H
O'Keefe
Regis J
RJ
D000818:Animals; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo / Q000187:drug effects* / Q000196:embryology; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D053823:Hedgehog Proteins; D018878:Limb Buds / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism; D009024:Morphogenesis / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology; D053773:Transforming Growth Factor beta1
D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D024121:Collagen Type X; D053823:Hedgehog Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D001973:Bromodeoxyuridine