Cb1 Enhanced Osteogenic Differentiation Of Bmscs By Rescue Mitochondrial Metabolism

CB1 is the main effector of endogenous cannabinoid system, and our previous study verified CB1 enhanced the osteo/dentinogenic differentiation of dental mesenchymal stem cells (MSCs), which might be a target for alveolar bone regeneration. In present study, we investigated the role and mechanism of CB1 on mitochondrial function and osteogenic differentiation of human bone marrow MSCs (hBMSCs) under inflammatory environment. ALP activity, ARS, quantitative calcium analysis, and osteogenic markers were used to detect the osteogenic differentiation ability of BMSCs. Real-time RT-PCR and Western blot were used to detect the gene expression. Mito Stress Test was used to detect the OCR. JC-10 assay was used to determine the mitochondrial membrane potential (MMP). CB1 increased osteogenic differentiation potential and mitochondrial energy metabolism, including the OCR, MMP, and enhanced the expressions of Nrf1 and Nrf2 in hBMSCs. Then, the inhibitor of mitochondrial electron transport chain (ETC), rotenone (ROT), inhibited the osteogenic differentiation in hBMSCs, and CB1 could rescue ROT impaired osteogenic differentiation potentials of hBMSCs . Activation of ETC by CoQ10 could restore the impaired osteogenic differentiation of hBMSCs by depletion of CB1. Mechanismly, CB1 activated the JNK signaling pathway, p38 MAPK signaling pathway, and inhibited the Erk1/2 signaling pathway. In conclusion, the activating of CB1 enhanced the osteogenic differentiation by rescued the mitochondrial metabolism function in hBMSCs under the inflammatory environment, suggesting that CB1 is a potential target for enhancing bone regeneration under the inflammatory environment.