Lin Li1, Jin Feng2, Lei Sun3, Yao-Wei Xuan1, Li Wen2, Yun-Xia Li2, Shuo Yang2, Biao Zhu4, Xiao-Yu Tian1, Shuang Li4, Li-Sheng Zhao2, Rui-Jie Dang2, Ting Jiao5, Hai-Song Zhang5, Ning Wen2. 1. Medical School of Chinese PLA, Beijing, China. 2. Department of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China. 3. Department of Stomatology, Medical Center of Chinese People's Liberation Army Strategic Support Force, Beijing, China. 4. Department of Stomatology, Fuxing Hospital, Capital Medical University, Beijing, China. 5. Department of Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, China.
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.
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.
Authors: Ke Sui; Kevin M Tveter; Fiona G Bawagan; Patricia Buckendahl; Savannah A Martinez; Zehra H Jaffri; Avery T MacDonell; Yue Wu; Rocio M Duran; Sue A Shapses; Diana E Roopchand Journal: Front Pharmacol Date: 2022-06-21 Impact factor: 5.988
Authors: Sophie Bradley; Scott Young; Anne Marie Bakke; Lucy Holcombe; Daniel Waller; Alysia Hunt; Kathleen Pinfold; Phillip Watson; Darren W Logan Journal: Front Vet Sci Date: 2022-09-21