RESUMEN
Bone marrow stromal/stem cells (BMSCs) are primitive and heterogeneous cells that can be differentiated into osteoblasts, adipocytes and other subsets. Their bone-fat lineage commitment is responsible for the homeostasis of bone marrow microenvironment. However, there are little effective methods and evidence to simultaneously visualise the lineage commitment of BMSCs. Here we provide a bivalent differentiation medium that can enable BMSCs differentiation into osteoblasts and adipocytes in vitro, and establish a method to simultaneously distinguish osteoblasts or adipocytes from the heterogeneous BMSCs based on Alizarin red S and Oil red O staining, which have been used for detection of specific mineralized nodules and lipid droplets, respectively. This assay provides a specifically simple but effective and low-cost method to evaluate the efficiency of osteo-adipogenic (OA) allocation of BMSCs.âºResearchers can utilize the bivalent differentiation medium to evaluate the efficiency of osteogenic and adipogenic differentiation of BMSCs in vitro.
RESUMEN
Bone marrow stromal/stem cells (BMSCs) are generally considered as common progenitors for both osteoblasts and adipocytes in the bone marrow, but show preferential differentiation into adipocytes rather than osteoblasts under aging, thus leading to senile osteoporosis. Accumulated evidences indicate that rejuvenation of BMSCs by autophagic enhancement delays bone aging. Here we synthetized and demonstrated a novel autophagy activator, CXM102 that could induce autophagy in aged BMSCs, resulting in rejuvenation and preferential differentiation into osteoblasts of BMSCs. Furthermore, CXM102 significantly stimulated bone anabolism, reduced marrow adipocytes, and delayed bone loss in middle-age male mice. Mechanistically, CXM102 promoted transcription factor EB (TFEB) nuclear translocation and favored osteoblasts formation both in vitro and in vivo. Moreover, CXM102 decreased serum levels of inflammation and reduced organ fibrosis, leading to a prolonger lifespan in male mice. Our results indicated that CXM102 could be used as an autophagy inducer to rejuvenate BMSCs and shed new lights on strategies for senile osteoporosis and healthyspan improvement.