| First Author | Okamura H | Year | 2011 |
| Journal | Bone | Volume | 49 |
| Issue | 3 | Pages | 368-75 |
| PubMed ID | 21683816 | Mgi Jnum | J:176987 |
| Mgi Id | MGI:5293271 | Doi | 10.1016/j.bone.2011.06.004 |
| Citation | Okamura H, et al. (2011) Reduction of protein phosphatase 2A Calpha enhances bone formation and osteoblast differentiation through the expression of bone-specific transcription factor Osterix. Bone 49(3):368-75 |
| abstractText | The serine/threonine protein phosphatase 2A (PP2A) participates in regulating many important physiological processes such as control of cell cycle, growth, and division. On the other hand, Osterix is a zinc-finger-containing transcription factor that is essential for the differentiation of osteoblasts and regulation of many bone-related genes. Here we examined the effect of okadaic acid (OA), a specific inhibitor of PP2A, on bone formation in vivo and the molecular mechanism regulated by PP2A Calpha in osteoblast differentiation. Administration of 1nM OA to the calvarial region in mice increased bone mineral density, as shown by muCT, while histomorphological analysis showed an increase in mineral apposition and bone thickness in the same region. In addition, treatment with 1nM OA stimulated osteoblast differentiation and the expression of Osterix, bone sialoprotein (Bsp), and osteocalcin (OCN) in mouse osteoblastic MC3T3-E1 cells. Moreover, the expression and phosphatase activity of PP2A Calpha was decreased in the initial step of osteoblast differentiation, which was in parallel with an increase in Osterix expression. To further clarify the role of PP2A Calpha in osteoblast differentiation, we constructed PP2A knock-down cells by infecting MC3T3-E1 cells with a lentivirus expressing shRNA specific for the PP2A Calpha. Accordingly, the silencing of PP2A Calpha in MC3T3-E1 cells dramatically increased osteoblast differentiation and mineralization, which were accompanied with expressions of Osterix, Bsp, and OCN. Our data indicate that PP2A Calpha plays an important role in the regulation of bone formation and osteoblast differentiation through the bone-related genes. |
