The spatiotemporal expression of TGF-β1 and its receptors during periosteal chondrogenesis in vitro

Hiroshi Mizuta, Arunik Sanyal, Takumi Fukumoto, James S. Fitzsimmons, Nobuzo Matsui, Mark E. Bolander, Merry Jo Oursler, Shawn W. O'Driscoll

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Abstract

Transforming growth factor-β1 (TGF-β1) has been shown to stimulate chondrogenesis in periosteal explants cultured in agarose suspension. TGF-βs exert their cellular effects through a heteromeric cell membrane receptor complex consisting of TGF-β type I and type II receptors. In this study, the spatial and temporal expressions of the type I receptor (TβR-I), type II receptor (TβR-II) and endogenous TGF-β1 in periosteal explants cultured in vitro were examined using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The temporal changes in the expression of the TβR-I and TβR-II mRNAs correlated with that of TGF-β1. Exogenous administration of TGF-β1 upregulated the expression of both receptors and of the TGF-β1 ligand in a biphasic pattern. The earlier peak of upregulation was observed at 7 days in culture. A later peak of upregulation was seen at 42 days, at which time cartilage formation reached a maximum. Immunohistochemical studies demonstrated co-localization of TβR-I and TβR-II simultaneously among the same cells expressing TGF-β1. TGF-β1 treatment increased the expression of TGF-β1, TβR-I and TβR-II in mesenchymal cells in the cambium layer at 7 days in culture. Small round chondrocytes showed widely distributed immunoreactivity of TGF-β1, TβR-I and TβR-II in the 42-day explants treated with TGF-β1. These observations support the hypothesis that TGF-β1 regulates the initiation and formation of cartilage during periosteal chondrogenesis.

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ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Mizuta, H., Sanyal, A., Fukumoto, T., Fitzsimmons, J. S., Matsui, N., Bolander, M. E., Oursler, M. J., & O'Driscoll, S. W. (2002). The spatiotemporal expression of TGF-β1 and its receptors during periosteal chondrogenesis in vitro. Journal of Orthopaedic Research, 20(3), 562-574. https://doi.org/10.1016/S0736-0266(01)00130-9