Zhang Dianying, Yu Kai, Yang Jie, Xie Shangding, Yang Jian, Tan Li
Department of Orthopedics and Trauma, People's Hospital, Peking University Beijing 100044, China.
Department of Orthopedics, Tianjin Fifth Central Hospital Tianjin 300450, China.
Am J Transl Res. 2020 Jun 15;12(6):3078-3088. eCollection 2020.
Bone marrow mesenchymal stem cells (BMSCs) are multipotential stem cells. Osteoporosis is an age-related disorder characterized by increased marrow fat accumulation and declined bone formation. Aging is an important initial factor of bone mass loss. So, manipulating the senescence of BMSCs is a considerable therapeutic target for osteoporosis treatment. To investigate the role of senolytics on regulating the differential fate of senescent BMSCs. Rat BMSCs were isolated and identified by immunofluorescence and multilineage differentiation assay. Quercetin was used to clean senescent BMSCs. Cell counting kit-8 (CCK-8) and colony formation assay was used to evaluate the cellular proliferation. While the cellular migration was detected by the scratch wound healing assay and transwell assay. And the osteogenesis assay and adipogenesis assay were used to determine the differential fate of BMSCs. BMSCs exhibited stemness. Eliminating senescent BMSCs improved the proliferation of BMSCs. But the quercetin treatment made no difference in cellular migration. And the osteogenic potential was increased while the adipogenic potential was decreased when the senescent BMSCs were cleaned by quercetin treatment. Our results demonstrate that cleaning senescent BMSCs improves the proliferation and osteogenesis of BMSCs as well as inhibits the adipogenesis of BMSCs, which provides a novel therapeutic target for the treatment of osteoporosis.
骨髓间充质干细胞（BMSCs）是多能干细胞。骨质疏松症是一种与年龄相关的疾病，其特征是骨髓脂肪堆积增加和骨形成减少。衰老是骨质流失的一个重要初始因素。因此，调控BMSCs的衰老状态是骨质疏松症治疗中一个值得关注的治疗靶点。为了研究衰老细胞溶解剂对调节衰老BMSCs不同命运的作用。通过免疫荧光和多谱系分化试验分离并鉴定大鼠BMSCs。使用槲皮素清除衰老的BMSCs。采用细胞计数试剂盒-8（CCK-8）和集落形成试验评估细胞增殖。同时，通过划痕伤口愈合试验和Transwell试验检测细胞迁移。并采用成骨试验和脂肪生成试验来确定BMSCs的不同命运。BMSCs表现出干性。清除衰老的BMSCs可改善BMSCs的增殖。但槲皮素处理对细胞迁移没有影响。当用槲皮素处理清除衰老的BMSCs时，成骨潜能增加，而脂肪生成潜能降低。我们的结果表明，清除衰老的BMSCs可改善BMSCs的增殖和成骨能力，并抑制BMSCs的脂肪生成，这为骨质疏松症的治疗提供了一个新的治疗靶点。
