Senolytic controls bone marrow mesenchymal stem cells fate improving bone formation

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.