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

doi:10.1038/nm.1979

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 journal › Article › peer-review

707 Scopus citations

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 language	English (US)
Pages (from-to)	757-765
Number of pages	9
Journal	Nature medicine
Volume	15
Issue number	7
DOIs	https://doi.org/10.1038/nm.1979
State	Published - Jul 2009
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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title = "TGF-Β1-induced migration of bone mesenchymal stem cells couples bone resorption with formation",

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.",

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

note = "Funding Information: The authors thank F. Hunter and T. Clemens for critical review and discussion of the manuscript and H.L. Moses (Vanderbilt University), C. Deng (US National Institutes of Health), J. Murphy-Ullrich (University of Alabama at Birmingham) and W. Xiong (Medical College of Georgia) for reagents. We thank the UAB Center for Metabolic Bone Disease Cores for mouse phenotyping, histomorphometry and molecular analyses. This research was supported by US National Institutes of Health grants AR 053973 and DK057501.",

year = "2009",

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doi = "10.1038/nm.1979",

language = "English (US)",

volume = "15",

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AU - Tang, Yi

AU - Wu, Xiangwei

AU - Lei, Weiqi

AU - Pang, Lijuan

AU - Wan, Chao

AU - Shi, Zhenqi

AU - Zhao, Ling

AU - Nagy, Timothy R.

AU - Peng, Xinyu

AU - Hu, Junbo

AU - Feng, Xu

AU - Van Hul, Wim

AU - Wan, Mei

AU - Cao, Xu

N1 - Funding Information: The authors thank F. Hunter and T. Clemens for critical review and discussion of the manuscript and H.L. Moses (Vanderbilt University), C. Deng (US National Institutes of Health), J. Murphy-Ullrich (University of Alabama at Birmingham) and W. Xiong (Medical College of Georgia) for reagents. We thank the UAB Center for Metabolic Bone Disease Cores for mouse phenotyping, histomorphometry and molecular analyses. This research was supported by US National Institutes of Health grants AR 053973 and DK057501.

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

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

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