TGF-Β1-induced migration of bone mesenchymal stem cells couples bone resorption with formation

Yi Tang, Xiangwei Wu, Weiqi Lei, Lijuan Pang, Chao Wan, Zhenqi Shi, Ling Zhao, Timothy R. Nagy, Xinyu Peng, Junbo Hu, Xu Feng, Wim Van Hul, Mei Wan, Xu Cao

Research output: Contribution to journalArticle

Abstract

Bone remodeling depends on the precise coordination of bone resorption and subsequent bone formation. Disturbances of this process are associated with skeletal diseases, such as Camurati-Engelmann disease (CED). We show using in vitro and in vivo models that active TGF-Β1 released during bone resorption coordinates bone formation by inducing migration of bone marrow stromal cells, also known as bone mesenchymal stem cells, to the bone resorptive sites and that this process is mediated through a SMAD signaling pathway. Analyzing mice carrying a CED-derived mutant TGFB1 (encoding TGF-Β1), which show the typical progressive diaphyseal dysplasia seen in the human disease, we found high levels of active TGF-Β1 in the bone marrow. Treatment with a TGF-Β type I receptor inhibitor partially rescued the uncoupled bone remodeling and prevented the fractures. Thus, as TGF-Β1 functions to couple bone resorption and formation, modulation of TGF-Β1 activity could be an effective treatment for bone remodeling diseases.

Original languageEnglish (US)
Pages (from-to)757-765
Number of pages9
JournalNature medicine
Volume15
Issue number7
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Tang, Y., Wu, X., Lei, W., Pang, L., Wan, C., Shi, Z., Zhao, L., Nagy, T. R., Peng, X., Hu, J., Feng, X., Van Hul, W., Wan, M., & Cao, X. (2009). TGF-Β1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nature medicine, 15(7), 757-765. https://doi.org/10.1038/nm.1979