| First Author | Masuda H | Year | 2014 |
| Journal | Bone | Volume | 58 |
| Pages | 1-10 | PubMed ID | 24096094 |
| Mgi Jnum | J:319027 | Mgi Id | MGI:6862397 |
| Doi | 10.1016/j.bone.2013.09.020 | Citation | Masuda H, et al. (2014) Anti-apoptotic Bcl-2 family member Mcl-1 regulates cell viability and bone-resorbing activity of osteoclasts. Bone 58:1-10 |
| abstractText | Myeloid cell leukemia sequence 1 (Mcl-1) is an anti-apoptotic Bcl-2 family protein and an immediate early gene expressed during myeloid leukemia cell line differentiation. We analyzed the expression and function of Mcl-1 in osteoclasts. Mcl-1 protein exhibited a short half-life in osteoclasts caused by its degradation in the ubiquitin-proteasome system. Mcl-1 had no effect on osteoclast differentiation, but its overexpression prolonged osteoclast survival and suppressed the bone-resorbing activity of these cells, as determined by pit formation assay. Conversely, Mcl-1 depletion suppressed osteoclast survival and increased bone resorption. This negative role for Mcl-1 on the bone-resorptive activities of osteoclasts may be caused by the increase in adenosine triphosphate/adenosine diphosphate ratio. Finally, we showed that the local deletion of Mcl-1 by the injection of the Cre adenovirus into the calvaria of Mcl1(fl/fl) mice significantly affected GST-RANKL-induced bone resorption in vivo. These results demonstrated that Mcl-1 positively regulates cell viability and negatively regulates the bone-resorbing activity of osteoclasts both in vitro and in vivo. |
