PP2A Regulatory Subunit B55γ is a Gatekeeper of Osteoblast Maturation and Lineage Maintenance
| Autor: | Else Munthe, Iwona Grad, Anastassia Serguienko, Ola Myklebost, Robert Hanes, Meng Yu Wang |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Cellular differentiation Morphogenesis Biology 03 medical and health sciences Receptors Glucocorticoid Glucocorticoid receptor Internal medicine Lipid droplet medicine Humans Cell Lineage Protein Phosphatase 2 Cells Cultured Gene knockdown Osteoblasts Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Osteoblast Lipid Droplets Cell Biology Hematology Cell biology Protein Subunits 030104 developmental biology medicine.anatomical_structure Endocrinology Female Bone marrow Developmental Biology |
| Zdroj: | Stem Cells and Development. 26:1375-1383 |
| ISSN: | 1557-8534 1547-3287 |
| DOI: | 10.1089/scd.2017.0129 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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