title: Protein phosphatase 2A Cα regulates osteoblast differentiation and the expressions of bone sialoprotein and osteocalcin via osterix transcription factor.
abstract: 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 α-isoform of PP2A catalytic subunit (PP2A Cα) accelerates osteoblast differentiation through the expression of bone-related genes. In this study, we further examined the role of PP2A Cα in osteoblast differentiation by establishing the stable cell lines that overexpress PP2A Cα. Overexpression of PP2A Cα reduced alkaline phosphatase (ALP) activity. Osteoblast differentiation and mineralization were also decreased in PP2A Cα-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 Cα-overexpressing cells. Introduction of ectopic Osterix rescued the expression of Bsp and OCN in PP2A Cα-overexpressing cells. These results indicate that PP2A Cα 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 Cα-mediated osteoblast differentiation.
authors.affiliation: Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan. okamura@dent.tokushima-u.ac.jp
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Okamura
authors.forename: Kaya
authors.initials: K
authors.lastname: Yoshida
authors.forename: Di
authors.initials: D
authors.lastname: Yang
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Haneji
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D058574:Integrin-Binding Sialoprotein / Q000378:metabolism*; D051379:Mice; D015675:Osteocalcin / Q000378:metabolism*; D010012:Osteogenesis; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D058574:Integrin-Binding Sialoprotein; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D015675:Osteocalcin; C578496:PPP2CA protein, mouse; D054648:Protein Phosphatase 2