| First Author | Yoshida K | Year | 2018 |
| Journal | Mol Cell Endocrinol | Volume | 470 |
| Pages | 251-258 | PubMed ID | 29128580 |
| Mgi Jnum | J:263347 | Mgi Id | MGI:6163942 |
| Doi | 10.1016/j.mce.2017.11.005 | Citation | Yoshida K, et al. (2018) Reduction of protein phosphatase 2A Calpha promotes in vivo bone formation and adipocyte differentiation. Mol Cell Endocrinol 470:251-258 |
| abstractText | Serine/threonine protein phosphatase 2A (PP2A) regulates diverse physiological processes such as cell cycle, growth, apoptosis, and signal transduction. Previously, we demonstrated that silencing of the alpha-isoform of PP2A catalytic subunit (PP2A Calpha) in osteoblasts accelerated osteoblast differentiation, whereas its overexpression suppressed differentiation. In this study, we examined the role of PP2A Calpha in in vivo bone formation by generating transgenic mice (PP2A-Tg), in which the dominant negative form of PP2A Calpha was specifically expressed in osteoblasts. PP2A-Tg mice exhibited an increase in body weight, cortical bone mineral density, and cortical bone thickness. Interestingly, they also displayed higher amounts of adipose tissue in the bone marrow of tibiae. The co-culture study showed that PP2A Calpha-knockdown osteoblasts stimulated adipocyte differentiation from undifferentiated mesenchymal cells via upregulation of the adipocyte marker genes, such as peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer binding protein alpha (C/EBPalpha). These results indicated that the reduction of PP2A Calpha levels in osteoblasts promoted bone formation in vivo. Additionally, PP2A Calpha in osteoblasts was also potentially involved in controlling adipocyte differentiation through a paracrine mechanism. |
