TY - JOUR
T1 - Transforming growth factor-β1 induced alteration of skeletal morphogenesis in vivo
AU - Ferguson, Cristin M.
AU - Schwarz, Edward M.
AU - Puzas, J. Edward
AU - Zuscik, Michael J.
AU - Drissi, Hicham
AU - O'Keefe, Regis J.
N1 - Funding Information:
We thank Cliff Tabin and Phoebe Leboy for in situ probes. We thank Diane Hu and Jill Helms for assistance with developmental biology and in situ techniques. This work was supported by an Orthopaedic Research Education Foundation Award (CMF) and National Institutes of Health Award R01 AR 38495 (RJO).
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
KW - Chondrocyte biology
KW - Chondrocyte maturation
KW - Chondrocyte proliferation
KW - Embryonic limb development
KW - Transforming growth factor-beta
UR - http://www.scopus.com/inward/record.url?scp=2942590939&partnerID=8YFLogxK
U2 - 10.1016/j.orthres.2003.10.023
DO - 10.1016/j.orthres.2003.10.023
M3 - Article
C2 - 15183422
AN - SCOPUS:2942590939
SN - 0736-0266
VL - 22
SP - 687
EP - 696
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
IS - 4
ER -