| First Author | Tang XL | Year | 2017 |
| Journal | Mol Cell Endocrinol | Volume | 439 |
| Pages | 203-212 | PubMed ID | 27614023 |
| Mgi Jnum | J:249260 | Mgi Id | MGI:6095313 |
| Doi | 10.1016/j.mce.2016.08.048 | Citation | Tang XL, et al. (2017) Protein tyrosine phosphatase SHP-1 modulates osteoblast differentiation through direct association with and dephosphorylation of GSK3beta. Mol Cell Endocrinol 439:203-212 |
| abstractText | SHP-1, the Src homology-2 (SH2) domain-containing phosphatase 1, is a cytosolic protein-tyrosine phosphatase (PTP) predominantly expressed in hematopoietic-derived cells. Previous studies have focused on the involvement of SHP-1 in osteoclastogenesis. Using primary cultured mouse fetal calvaria-derived osteoblasts as a model, this study aims to investigate the effects of SHP-1 on differentiation and mineralization of osteoblasts and elucidate the signaling pathways responsible for these effects. We found that osteoblasts treated by osteogenic media showed significant increase in SHP-1 expression, which contributed to osteoblastic differentiation and mineralization. Using immunoprecipitation assay, we found that a direct association between SHP-1 and glycogen synthase kinase (GSK)-3beta could be detected in differentiated osteoblasts and was significantly inhibited by SHP-1 inhibitor NSC87877. Inhibition of SHP-1 activated GSK3beta, thereby leading to suppression of osteoblast differentiation and mineralization, which could be rescued by the inhibitor of GSK3beta. In addition, we found that rosiglitazone (RSG) treatment led to significant decrease in SHP-1 expression. Overexpression of SHP-1 reversed RSG-induced GSK3beta activation, thus rescuing the inhibitory effect of RSG on osteoblast differentiation and mineralization. These findings suggest that protein tyrosine phosphatase SHP-1 may act as a positive regulator of osteoblast differentiation through direct association with and dephosphorylation of GSK3beta. Downregulation of SHP-1 may contribute to RSG-induced inhibition of mouse calvaria osteoblast differentiation by activating GSK3beta-dependent pathway. |
