| First Author | Chen Q | Year | 2014 |
| Journal | Stem Cells | Volume | 32 |
| Issue | 2 | Pages | 327-37 |
| PubMed ID | 24123709 | Mgi Jnum | J:206759 |
| Mgi Id | MGI:5551947 | Doi | 10.1002/stem.1567 |
| Citation | Chen Q, et al. (2014) An osteopontin-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells. Stem Cells 32(2):327-37 |
| abstractText | 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 alphav/beta1 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 alphav/beta1 but not CD44 also affected MSC differentiation. Further studies revealed that OPN inhibits the C/EBPs signaling pathway through integrin alphav/beta1. 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 alphav/beta1 in regulating MSC differentiation. |
