SHP1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Differentiation
Menghui Jiang,
Chunxing Zheng,
Peishun Shou,
Na Li,
Gang Cao,
Qing Chen,
Chunliang Xu,
Liming Du,
Qian Yang,
Jianchang Cao,
Yanyan Han,
Fengying Li,
Wei Cao,
Feng Liu,
Arnold B. Rabson,
Arthur I. Roberts,
Weifen Xie,
Ying Wang,
Yufang Shi
Affiliations
Menghui Jiang
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Chunxing Zheng
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Peishun Shou
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Na Li
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Gang Cao
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Qing Chen
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Chunliang Xu
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Liming Du
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Qian Yang
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Jianchang Cao
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Yanyan Han
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Fengying Li
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Wei Cao
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Feng Liu
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Arnold B. Rabson
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 80903, USA
Arthur I. Roberts
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 80903, USA
Weifen Xie
Changzheng Hospital, the Second Military Medical University, Shanghai 200433, China
Ying Wang
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Yufang Shi
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Osteoblasts and adipocytes are derived from a common precursor, mesenchymal stem cells (MSCs). Alterations in the normal fate of differentiating MSCs are involved in the development of obesity and osteoporosis. Here, we report that viable motheaten (mev) mice, which are deficient in the SH2-domain-containing phosphatase-1 (SHP1), develop osteoporosis spontaneously. Consistently, MSCs from mev/mev mice exhibit significantly reduced osteogenic potential and greatly increased adipogenic potential. When MSCs were transplanted into nude mice, SHP1-deficient MSCs resulted in diminished bone formation compared with wild-type MSCs. SHP1 was found to bind to GSK3β and suppress its kinase activity by dephosphorylating pY216, thus resulting in β-catenin stabilization. Mice, in which SHP1 was deleted in MSCs using SHP1fl/flDermo1-cre, displayed significantly decreased bone mass and increased adipose tissue. Taken together, these results suggest a possible role for SHP1 in controlling tissue homeostasis through modulation of MSC differentiation via Wnt signaling regulation.
