PP2A Regulatory Subunit B55γ is a Gatekeeper of Osteoblast Maturation and Lineage Maintenance.

Bone marrow mesenchymal stem cells (BM-MSCs) mediate skeletal remodeling by differentiating into osteoblasts. However, this remodeling is impaired with aging as well as following long-term glucocorticoid treatment, resulting in osteoporosis. In this study, we report a novel factor of osteoblast differentiation-PP2A regulatory subunit B55γ. We show that B55γ is induced by glucocorticoid receptor (GR) in human primary BM-MSCs during differentiation to osteoblast, but not to adipocytes, and is required for osteoblast morphogenesis and mineralization. Moreover, B55γ knockdown under osteogenic conditions leads to the accumulation of lipid droplets in a subset of BM-MSCs. Treatment of BM-MSCs with only GR ligand dexamethasone induces B55γ transcript, but not protein, and causes widespread generation of lipid droplets. These data indicate that B55γ is an essential factor of osteoblast lineage, acting as a gatekeeper downstream of master regulators. This opens a new direction of research for understanding mechanisms of glucocorticoid-induced osteoporosis and bone marrow adiposity.