| First Author | Moon YJ | Year | 2016 |
| Journal | Exp Mol Med | Volume | 48 |
| Issue | 9 | Pages | e256 |
| PubMed ID | 27585718 | Mgi Jnum | J:317671 |
| Mgi Id | MGI:6844179 | Doi | 10.1038/emm.2016.75 |
| Citation | Moon YJ, et al. (2016) Smad4 controls bone homeostasis through regulation of osteoblast/osteocyte viability. Exp Mol Med 48(9):e256 |
| abstractText | Regulation of osteoblast and osteocyte viability is essential for bone homeostasis. Smad4, a major transducer of bone morphogenetic protein and transforming growth factor-beta signaling pathways, regulates apoptosis in various cell types through a mitochondrial pathway. However, it remains poorly understood whether Smad4 is necessary for the regulation of osteoblast and osteocyte viability. In this study, we analyzed Smad4Delta(Os) mice, in which Smad4 was subjected to tissue-specific disruption under the control of the 2.3-kb Col1a1 promoter, to understand the functional significance of Smad4 in regulating osteoblast/osteocyte viability during bone formation and remodeling. Smad4Delta(Os) mice showed a significant increase in osteoblast number and osteocyte density in the trabecular and cortical regions of the femur, whereas osteoclast activity was significantly decreased. The proliferation of osteoblasts/osteocytes did not alter, as shown by measuring 5'-bromo-2'deoxyuridine incorporation. By contrast, the percentage of TUNEL-positive cells decreased, together with a decrease in the Bax/Bcl-2 ratio and in the proteolytic cleavage of caspase 3, in Smad4Delta(Os) mice. Apoptosis in isolated calvaria cells from Smad4Delta(Os) mice decreased after differentiation, which was consistent with the results of the TUNEL assay and western blotting in Smad4Delta(Os) mice. Conversely, osteoblast cells overexpressing Smad4 showed increased apoptosis. In an apoptosis induction model of Smad4Delta(Os) mice, osteoblasts/osteocytes were more resistant to apoptosis than were control cells, and, consequently, bone remodeling was attenuated. These findings indicate that Smad4 has a significant role in regulating osteoblast/osteocyte viability and therefore controls bone homeostasis. |
