PP2A Regulatory Subunit B55 is a Gatekeeper of Osteoblast Maturation and Lineage Maintenance
PP2A Regulatory Subunit B55 is a Gatekeeper of Osteoblast Maturation and Lineage Maintenance
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DOI：
10.1089/scd.2017.0129
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发表时间：
2017-10-01
影响因子：
4
通讯作者：
Munthe, Else
中科院分区：
文献类型：
--
作者：
Serguienko, Anastassia;Hanes, Robert;Munthe, Else
骨髓间充质干细胞（BM-MSCs）通过向成骨细胞分化介导骨重建。然而，这种重塑随着年龄的增长以及长期糖皮质激素治疗而受损，导致骨质疏松症。在本研究中，我们报道了一种新的成骨细胞分化因子--PP 2A调节亚基B55。我们表明，B55 γ诱导的糖皮质激素受体（GR）在人原代BM-MSCs分化成骨细胞，但不是脂肪细胞，成骨细胞形态发生和矿化所需的。此外，在成骨条件下B55 γ敲低导致BM-MSC亚组中脂滴的积累。仅用GR配体地塞米松处理BM-MSC诱导B55 γ转录物，但不诱导蛋白质，并引起脂滴的广泛产生。这些数据表明，B55 γ是成骨细胞谱系的一个重要因素，作为主调节器下游的看门人。这为了解糖皮质激素诱导的骨质疏松和骨髓肥胖的机制开辟了一个新的研究方向。
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 B55. We show that B55 gamma 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, B55 gamma 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 B55 gamma transcript, but not protein, and causes widespread generation of lipid droplets. These data indicate that B55 gamma 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.