| First Author | Holm CK | Year | 2016 |
| Journal | Biochem Biophys Res Commun | Volume | 478 |
| Issue | 1 | Pages | 268-273 |
| PubMed ID | 27422603 | Mgi Jnum | J:238666 |
| Mgi Id | MGI:5823331 | Doi | 10.1016/j.bbrc.2016.07.048 |
| Citation | Holm CK, et al. (2016) Lack of SIRPalpha phosphorylation and concomitantly reduced SHP-2-PI3K-Akt2 signaling decrease osteoblast differentiation. Biochem Biophys Res Commun 478(1):268-73 |
| abstractText | Normal differentiation of bone forming osteoblasts is a prerequisite for maintenance of skeletal health and is dependent on intricate cellular signaling pathways, including the essential transcription factor Runx2. The cell surface glycoprotein CD47 and its receptor signal regulatory protein alpha (SIRPalpha) have both been suggested to regulate bone cell differentiation. Here we investigated osteoblastic differentiation of bone marrow stromal cells from SIRPalpha mutant mice lacking the cytoplasmic signaling domain of SIRPalpha. An impaired osteoblastogenesis in SIRPalpha-mutant cell cultures was demonstrated by lower alkaline phosphatase activity and less mineral formation compared to wild-type cultures. This reduced osteoblastic differentiation potential in SIRPalpha-mutant stromal cells was associated with a significantly reduced expression of Runx2, osterix, osteocalcin, and alkaline phosphatase mRNA, as well as a reduced phosphorylation of SHP-2 and Akt2, as compared with that in wild-type stromal cells. Addition of a PI3K-inhibitor to wild-type stromal cells could mimic the impaired osteoblastogenesis seen in SIRPalpha-mutant cells. In conclusion, our data suggest that SIRPalpha signaling through SHP-2-PI3K-Akt2 strongly influences osteoblast differentiation from bone marrow stromal cells. |
