SHP1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Differentiation

被引：23

作者：

Jiang, Menghui ^{[1
,2
]}

Zheng, Chunxing ^{[1
,2
]}

Shou, Peishun ^{[1
,2
]}

Li, Na ^{[1
,2
]}

Cao, Gang ^{[1
,2
]}

Chen, Qing ^{[1
,2
]}

Xu, Chunliang ^{[1
,2
]}

Du, Liming ^{[1
,2
]}

Yang, Qian ^{[1
,2
]}

Cao, Jianchang ^{[1
,2
]}

Han, Yanyan ^{[1
,2
]}

Li, Fengying ^{[1
,2
]}

Cao, Wei ^{[1
,2
]}

Liu, Feng ^{[1
,2
]}

Rabson, Arnold B. ^{[4
]}

Roberts, Arthur I. ^{[4
]}

Xie, Weifen ^{[5
]}

Wang, Ying ^{[1
,2
]}

Shi, Yufang ^{[1
,2
,3
,4
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

[3] Soochow Univ, Inst Translat Med, Affiliated Hosp 3, Suzhou 215006, Peoples R China

[4] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA

[5] Second Mil Med Univ, Changzheng Hosp, Shanghai 200433, Peoples R China

来源：

CELL REPORTS | 2016年 / 16卷 / 03期

关键词：

TYROSINE PHOSPHATASE SHP-1; OSTEOBLAST DIFFERENTIATION; NEGATIVE REGULATION; PROTEIN; BETA; ADIPOGENESIS; REGENERATION; DEFICIENCY; WNT10B; MOUSE;

D O I：

10.1016/j.celrep.2016.06.035

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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 GSK3 beta and suppress its kinase activity by dephosphorylating pY216, thus resulting in beta-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.

引用

页码：769 / 780

页数：12

共 43 条

[1]

The tyrosine phosphatase SHP-1 is a negative regulator of osteoclastogenesis and osteoclast resorbing activity:: Increased resorption and osteopenia in mev/mev mutant mice [J].