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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)\n 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CB1 increased osteogenic differentiation potential and mitochondrial energy metabolism, including the OCR, MMP, and enhanced the expressions of\n                      <jats:italic>Nrf1<\/jats:italic>\n                      and\n                      <jats:italic>Nrf2<\/jats:italic>\n                      in hBMSCs without or with TNF-\u03b1 or INF-\u03b3 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-\u03b1 or INF-\u03b3 stimulation. Activation of ETC by Coenzyme Q10 (CoQ10) could restore the impaired osteogenic differentiation of hBMSCs by depletion of CB1 without or with TNF-\u03b1 or INF-\u03b3 stimulation. Mechanismly, CB1 could activate the JNK signaling pathway, p38 MAPK signaling pathway, and inhibit the Erk1\/2 signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-022-02702-9","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T05:03:22Z","timestamp":1642741402000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["The cannabinoid receptor I (CB1) enhanced the osteogenic differentiation of BMSCs by rescue impaired mitochondrial metabolism function under inflammatory condition"],"prefix":"10.1186","volume":"13","author":[{"given":"Wanhao","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengqiu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1662-9420","authenticated-orcid":false,"given":"Zhipeng","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"2702_CR1","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.reth.2019.12.011","volume":"14","author":"T Ouchi","year":"2020","unstructured":"Ouchi T, Nakagawa T. 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