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

Research output: Contribution to journalArticle

11 Scopus citations

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 (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.

Original languageEnglish (US)
Pages (from-to)769-780
Number of pages12
JournalCell Reports
Volume16
Issue number3
DOIs
StatePublished - Jul 19 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Jiang, M., Zheng, C., Shou, P., Li, N., Cao, G., Chen, Q., Xu, C., Du, L., Yang, Q., Cao, J., Han, Y., Li, F., Cao, W., Liu, F., Rabson, A. B., Roberts, A. I., Xie, W., Wang, Y., & Shi, Y. (2016). SHP1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Differentiation. Cell Reports, 16(3), 769-780. https://doi.org/10.1016/j.celrep.2016.06.035