The cannabinoid receptor I (CB1) enhanced the osteogenic differentiation of BMSCs by rescue impaired mitochondrial metabolism function under inflammatory condition

Stem Cell Research & Therapy

Fengqiu Zhang¹  Wanhao Yan²  Lihua Ge²  Zhipeng Fan²  Lei Hu³  Le Li⁴ 

[1] Department of Periodontology, Capital Medical University School of Stomatology;Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology;Salivary Gland Disease Center and Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology;Tsinghua University Hospital, Stomatological Disease Prevention and Control Center, Tsinghua University;

关键词: CB1;    Bone marrow mesenchymal stem cells (BMSCs);    Mitochondrial metabolism;    Osteogenic differentiation;    Inflammation;   

DOI  :  10.1186/s13287-022-02702-9

来源: DOAJ

【 摘 要 】

Abstract Background Periodontitis is a chronic infectious disease leading to bone resorption and periodontal tissue disruption under inflammatory stimulation. The osteogenic differentiation ability of mesenchymal stem cells (MSCs) is impaired under the inflammatory environment, which limits the effect of treatment. The cannabinoid receptor I (CB1) is the main effector of the endogenous cannabinoid system (ECS), and our previous study verified that CB1 could enhance the osteo/dentinogenic differentiation of dental MSCs, which might be a target for alveolar bone regeneration. However, the effect of CB1 on the osteogenic differentiation of MSCs derived from bone remains unknown. In present study, we investigated the role and mechanism of CB1 on mitochondrial function and osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) under inflammatory environment. Methods Alkaline phosphatase (ALP) activity, alizarin red staining, 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. Seahorse Cell Mito Stress Test was used to detect the oxygen consumption rate (OCR). JC-10 assay was used to determine the mitochondrial membrane potential (MMP). Results CB1 increased osteogenic differentiation potential and mitochondrial energy metabolism, including the OCR, MMP, and enhanced the expressions of Nrf1 and Nrf2 in hBMSCs without or with TNF-α or INF-γ stimulation. 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 without or with TNF-α or INF-γ stimulation. Activation of ETC by Coenzyme Q10 (CoQ10) could restore the impaired osteogenic differentiation of hBMSCs by depletion of CB1 without or with TNF-α or INF-γ stimulation. Mechanismly, CB1 could activate the JNK signaling pathway, p38 MAPK signaling pathway, and inhibit the Erk1/2 signaling pathway. Conclusions The activating of CB1 enhanced the osteogenic differentiation by rescuing 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.

【 授权许可】

Unknown