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

被引：911

作者：

Tang, Yi ^{[1
]}

Wu, Xiangwei ^{[1
,2
,3
]}

Lei, Weiqi ^{[1
]}

Pang, Lijuan ^{[1
,4
]}

Wan, Chao ^{[1
]}

Shi, Zhenqi ^{[1
]}

Zhao, Ling ^{[1
]}

Nagy, Timothy R. ^{[5
]}

Peng, Xinyu ^{[3
]}

Hu, Junbo ^{[2
]}

Feng, Xu ^{[1
]}

Van Hul, Wim ^{[6
]}

Wan, Mei ^{[1
]}

Cao, Xu ^{[1
]}

机构：

[1] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA

[2] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Wuhan, Hubei, Peoples R China

[3] Shihezi Univ, Sch Med, Affiliated Hosp 1, Shihezi, Xinjiang, Peoples R China

[4] Shihezi Univ, Sch Med, Dept Pathol, Shihezi, Xinjiang, Peoples R China

[5] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA

[6] Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium

来源：

NATURE MEDICINE | 2009年 / 15卷 / 07期

基金：

美国国家卫生研究院;

关键词：

GROWTH-FACTOR-BETA; CAMURATI-ENGELMANN-DISEASE; LATENCY-ASSOCIATED PEPTIDE; DOMAIN-SPECIFIC MUTATIONS; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; DIFFERENT POPULATIONS; ACTIVATION; COMPLEX; MATRIX;

D O I：

10.1038/nm.1979

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-beta 1 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-beta 1), which show the typical progressive diaphyseal dysplasia seen in the human disease, we found high levels of active TGF-beta 1 in the bone marrow. Treatment with a TGF-beta type I receptor inhibitor partially rescued the uncoupled bone remodeling and prevented the fractures. Thus, as TGF-beta 1 functions to couple bone resorption and formation, modulation of TGF-beta 1 activity could be an effective treatment for bone remodeling diseases.

引用

页码：757 / U9

页数：10

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