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SHP1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Differentiation
Menghui Jiang1, Chunxing Zheng1, Peishun Shou1
1Key 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.
Cell Reports
|July 12, 2016
Summary
SHP1 deficiency in mice leads to osteoporosis and increased fat. This phosphatase regulates mesenchymal stem cell differentiation, impacting bone formation and fat storage.
Area of Science:
- Cell Biology
- Stem Cell Research
- Bone Biology
Background:
- Mesenchymal stem cells (MSCs) differentiate into osteoblasts and adipocytes.
- Dysregulation of MSC differentiation contributes to obesity and osteoporosis.
- SHP1 (SH2-domain-containing phosphatase-1) role in MSC fate is not fully understood.
Purpose of the Study:
- Investigate the role of SHP1 in regulating MSC differentiation.
- Determine the impact of SHP1 deficiency on bone mass and adipose tissue.
- Elucidate the molecular mechanism by which SHP1 influences MSC fate.
Main Methods:
- Utilized viable motheaten (me(v)) mice deficient in SHP1.
- Assessed osteogenic and adipogenic potential of MSCs from me(v)/me(v) mice.
- Transplanted SHP1-deficient MSCs into nude mice.
- Generated mice with SHP1 deleted in MSCs using SHP1(fl/fl)Dermo1-cre.
- Investigated SHP1 interaction with GSK3β and its effect on β-catenin signaling.
Main Results:
- SHP1-deficient mice spontaneously developed osteoporosis.
- MSCs from SHP1-deficient mice showed reduced osteogenesis and increased adipogenesis.
- Transplantation of SHP1-deficient MSCs led to diminished bone formation.
- SHP1 deficiency in MSCs resulted in decreased bone mass and increased adipose tissue.
- SHP1 dephosphorylates pY216 of GSK3β, suppressing its activity and stabilizing β-catenin.
Conclusions:
- SHP1 plays a crucial role in maintaining tissue homeostasis by controlling MSC differentiation.
- SHP1 modulates MSC fate via regulation of the Wnt signaling pathway.
- Targeting SHP1 may offer therapeutic strategies for obesity and osteoporosis.
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