期刊
STEM CELLS
卷 32, 期 2, 页码 327-337出版社
WILEY
DOI: 10.1002/stem.1567
关键词
Adipocytes; Osteoblasts; Integrins; C; EBP; Differentiation
资金
- Ministry of Science and Technology of China [2010CB945600, 2011DFA30630]
- Scientific Innovation Project of the Chinese Academy of Science [XDA010 40107]
- National Science and Technology Project of China [31010103908]
- National Institutes of Health of the United States of America [DE014913, DE019932, GM866889]
An imbalance between normal adipogenesis and osteogenesis by mesenchymal stem cells (MSCs) has been shown to be related to various human metabolic diseases, such as obesity and osteoporosis; however, the underlying mechanisms remain elusive. We found that the interaction between osteopontin (OPN), an arginine-glycine-aspartate-containing glycoprotein, and integrin v/1 plays a critical role in the lineage determination of MSCs. Although OPN is a well-established marker during osteogenesis, its role in MSC differentiation is still unknown. Our study reveals that blockade of OPN function promoted robust adipogenic differentiation, while inhibiting osteogenic differentiation. Re-expression of OPN restored a normal balance between adipogenesis and osteogenesis in OPN-/- MSCs. Retarded bone formation by OPN-/- MSCs was also verified by in vivo implantation with hydroxyapatite-tricalcium phosphate, a bone-forming matrix. The role of extracellular OPN in MSC differentiation was further demonstrated by supplementation and neutralization of OPN. Blocking well-known OPN receptors integrin v/1 but not CD44 also affected MSC differentiation. Further studies revealed that OPN inhibits the C/EBPs signaling pathway through integrin v/1. Consistent with these in vitro results, OPN-/- mice had a higher fat to total body weight ratio than did wild-type mice. Therefore, our study demonstrates a novel role for OPN-integrin v/1 in regulating MSC differentiation. Stem Cells2014;32:327-337
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