title: SHP1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Differentiation.
abstract: 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 (me(v)) mice, which are deficient in the SH2-domain-containing phosphatase-1 (SHP1), develop osteoporosis spontaneously. Consistently, MSCs from me(v)/me(v) 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 SHP1(fl/fl)Dermo1-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.
authors.affiliation: 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.
authors.forename: Menghui
authors.initials: M
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Chunxing
authors.initials: C
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Peishun
authors.initials: P
authors.lastname: Shou
authors.affiliation: 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.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Gang
authors.initials: G
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Chunliang
authors.initials: C
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Liming
authors.initials: L
authors.lastname: Du
authors.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Jianchang
authors.initials: J
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Fengying
authors.initials: F
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 80903, USA.
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Rabson
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 80903, USA.
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Roberts
authors.affiliation: Changzheng Hospital, the Second Military Medical University, Shanghai 200433, China.
authors.forename: Weifen
authors.initials: W
authors.lastname: Xie
authors.affiliation: 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. Electronic address: yingwang@sibs.ac.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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; The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou 215006, China; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 80903, USA. Electronic address: yufangshi@sibs.ac.cn.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D015519:Bone Density / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6