| Literature DB >> 27396328 |
Menghui Jiang1, Chunxing Zheng1, Peishun Shou1, Na Li1, Gang Cao1, Qing Chen1, Chunliang Xu1, Liming Du1, Qian Yang1, Jianchang Cao1, Yanyan Han1, Fengying Li1, Wei Cao1, Feng Liu1, Arnold B Rabson2, Arthur I Roberts2, Weifen Xie3, Ying Wang4, Yufang Shi5.
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.Entities:
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Year: 2016 PMID： 27396328 DOI： 10.1016/j.celrep.2016.06.035
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423