Protein phosphatase 2A Cα regulates osteoblast differentiation and the expressions of bone sialoprotein and osteocalcin via osterix transcription factor

Serine/threonine protein phosphatase 2A (PP2A) participates in regulating many important physiological processes such as cell cycle, growth, apoptosis, and signal transduction. Osterix is a zinc-finger-containing transcription factor that is essential for osteoblast differentiation and regulation of many bone-related genes. We have recently reported that decrease in a-isoform of PP2A catalytic subunit (PP2A Ca) accelerates osteoblast differentiation through the expression of bone-related genes. In this study, we further examined the role of PP2A Ca in osteoblast differentiation by establishing the stable cell lines that overexpress PP2A Ca. Overexpression of PP2A Ca reduced alkaline phosphatase (ALP) activity. Osteoblast differentiation and mineralization were also decreased in PP2A Ca-overexpressing cells, with reduction of bone-related genes including osterix, bone sialoprotein (Bsp), and osteocalcin (OCN). Luciferase assay showed that the transcriptional activity of the Osterix promoter region was decreased in PP2A Ca-overexpressing cells. Introduction of ectopic Osterix rescued the expression of Bsp and OCN in PP2A Ca-overexpressing cells. These results indicate that PP2A Ca and its activity play a negative role in osteoblast differentiation and Osterix is a key factor responsible for regulating the expressions of Bsp and OCN during PP2A Ca-mediated osteoblast differentiation. J. Cell. Physiol. (C) 2012 Wiley Periodicals, Inc.