International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Cannabidiol Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in the Inflammatory Microenvironment via the CB2-dependent p38 MAPK Signaling Pathway

  • Lin Li (Medical School of Chinese PLA) ;
  • Jin Feng (Department of Stomatology, The First Medical Center, Chinese PLA General Hospital) ;
  • Lei Sun (Department of Stomatology, Medical Center of Chinese People's Liberation Army Strategic Support Force) ;
  • Yao-wei Xuan (Medical School of Chinese PLA) ;
  • Li Wen (Department of Stomatology, The First Medical Center, Chinese PLA General Hospital) ;
  • Yun-xia Li (Department of Stomatology, The First Medical Center, Chinese PLA General Hospital) ;
  • Shuo Yang (Department of Stomatology, The First Medical Center, Chinese PLA General Hospital) ;
  • Biao Zhu (Department of Stomatology, Fuxing Hospital, Capital Medical University) ;
  • Xiao-yu Tian (Medical School of Chinese PLA) ;
  • Shuang Li (Department of Stomatology, Fuxing Hospital, Capital Medical University) ;
  • Li-sheng Zhao (Department of Stomatology, The First Medical Center, Chinese PLA General Hospital) ;
  • Rui-jie Dang (Department of Stomatology, The First Medical Center, Chinese PLA General Hospital) ;
  • Ting Jiao (Department of Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy) ;
  • Hai-song Zhang (Department of Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy) ;
  • Ning Wen (Department of Stomatology, The First Medical Center, Chinese PLA General Hospital)
  • Received : 2021.09.07
  • Accepted : 2022.01.04
  • Published : 2022.11.30
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Abstract

Background and Objectives: Chronic inflammation of bone tissue often results in bone defects and hazards to tissue repair and regeneration. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including anti-inflammatory and osteogenic potential. This study aimed to investigate the efficacy and mechanisms of CBD in the promotion of bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in the inflammatory microenvironment. Methods and Results: BMSCs isolated from C57BL/6 mice, expressed stem cell characteristic surface markers and presented multidirectional differentiation potential. The CCK-8 assay was applied to evaluate the effects of CBD on BMSCs' vitality, and demonstrating the safety of CBD on BMSCs. Then, BMSCs were stimulated with lipopolysaccharide (LPS) to induce inflammatory microenvironment. We found that CBD intervention down-regulated mRNA expression levels of inflammatory cytokines and promoted cells proliferation in LPS-treated BMSCs, also reversed the protein and mRNA levels downregulation of osteogenic markers caused by LPS treatment. Moreover, CBD intervention activated the cannabinoid receptor 2 (CB2) and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. While AM630, a selective CB2 inhibitor, reduced phosphorylated (p)-p38 levels. In addition, AM630 and SB530689, a selective p38 MAPK inhibitor, attenuated the enhancement of osteogenic markers expression levels by CBD in inflammatory microenvironment, respectively. Conclusions: CBD promoted osteogenic differentiation of BMSCs via the CB2/p38 MAPK signaling pathway in the inflammatory microenvironment.

Keywords

Acknowledgement

This work was supported by grants from Project funded by China Postdoctoral Science Foundation (2019T120980, 2018M633722) and National Natural Science Foundation of China (NSFC51802350, NSFC51972339).

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