Osteoporosis is a commonly seen degenerative bone disorder in the elderly and postmenopausal women, with a low bone mineral density as a major risk factor. The osteogenic potential of bone marrow stromal cells (BMSCs) showed to be impaired during osteoporosis. We established a postmenopausal osteoporosis model in ovariectomized (OVX) mice and found the upregulation of proteasome 26S subunit ATPase 2 (PSMC2) in OVX mice. PSMC2 silencing improved OVX-impaired biomechanical properties of mice femur, OVX-decreased BMD, and OVX-destroyed bone structure. Histopathological analysis indicated that PSMC2 silencing improved bone trabecular structure and increased the contents of collagen fibers and newly formed bone or cartilage in OVX mice. In the meantime, PSMC2 silencing increased Runx2, PI3K, Wnt3a, and β-catenin protein contents while reduced CTSK protein. Within BMSCs isolated from OVX mice, PSMC2 silencing promoted BMSC osteogenic differentiation and elevated osteogenic markers’ protein contents, including HOXA10, Runx2, OCN, OPN, and COL1A2. In conclusion, PSMC2 expression is upregulated in the postmenopausal osteoporosis model in OVX mice. PSMC2 silencing promotes the osteogenic differentiation of BMSCs in vitro, promotes bone formation, and inhibits bone resorption in vivo.

骨质疏松症是老年人和绝经后妇女常见的退行性骨病，骨密度低是主要危险因素。骨髓基质细胞 (BMSCs) 的成骨潜能在骨质疏松症期间显示受损。我们在去卵巢 (OVX) 小鼠中建立了绝经后骨质疏松模型，并发现 OVX 小鼠中蛋白酶体 26S 亚基 ATPase 2 (PSMC2) 的上调。PSMC2 沉默改善了 OVX 受损的小鼠股骨生物力学特性、OVX 降低的 BMD 和 OVX 破坏的骨结构。组织病理学分析表明，PSMC2 沉默改善了 OVX 小鼠的骨小梁结构并增加了胶原纤维和新形成的骨或软骨的含量。与此同时，PSMC2 沉默增加了 Runx2、PI3K、Wnt3a、和 β-catenin 蛋白含量同时降低 CTSK 蛋白。在从 OVX 小鼠分离的 BMSCs 中，PSMC2 沉默促进了 BMSC 成骨分化并提高了成骨标志物的蛋白质含量，包括 HOXA10、Runx2、OCN、OPN 和 COL1A2。总之，PSMC2 表达在 OVX 小鼠绝经后骨质疏松模型中上调。PSMC2 沉默在体外促进 BMSCs 的成骨分化，促进骨形成，并在体内抑制骨吸收。