| First Author | Bao Q | Year | 2017 |
| Journal | Exp Cell Res | Volume | 350 |
| Issue | 1 | Pages | 123-131 |
| PubMed ID | 27865936 | Mgi Jnum | J:260888 |
| Mgi Id | MGI:6151922 | Doi | 10.1016/j.yexcr.2016.11.013 |
| Citation | Bao Q, et al. (2017) Constitutive beta-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality. Exp Cell Res 350(1):123-131 |
| abstractText | Accumulating evidence suggests that Wnt/beta-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of beta-catenin (CA-beta-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-beta-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-beta-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-beta-catenin mice. Then the effect of CA-beta-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-beta-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-beta-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-beta-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-beta-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-beta-catenin mice. In summary, osteoblastic CA-beta-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength. |
