TGF-β1-induced migration of bone mesenchymal stem cells couples bone resorption with formation

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

Affiliations

¹Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA

²Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

³First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang, China

⁴Department of Pathology, School of Medicine, Shihezi University, Shihezi, Xinjiang, China

⁵Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA

⁶Department of Medical Genetics, University of Antwerp, Antwerp, Belgium

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.

Links

DOI: 10.1038/nm.1979

PubMed: 19584867

PubMedCentral: PMC2727637

WoS: 000267806900028

History

Received: 2008-08-05

Accepted: 2009-05-05

Online: 2009-07-05

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