PMID- 35220282
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221207
IS  - 2005-3606 (Print)
IS  - 2005-5447 (Electronic)
IS  - 2005-3606 (Linking)
VI  - 15
IP  - 4
DP  - 2022 Nov 30
TI  - Cannabidiol Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem 
      Cells in the Inflammatory Microenvironment via the CB2-dependent p38 MAPK 
      Signaling Pathway.
PG  - 405-414
LID - 10.15283/ijsc21152 [doi]
AB  - 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.
FAU - Li, Lin
AU  - Li L
AD  - Medical School of Chinese PLA, Beijing, China.
FAU - Feng, Jin
AU  - Feng J
AD  - Department of Stomatology, The First Medical Center, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Sun, Lei
AU  - Sun L
AD  - Department of Stomatology, Medical Center of Chinese People's Liberation Army 
      Strategic Support Force, Beijing, China.
FAU - Xuan, Yao-Wei
AU  - Xuan YW
AD  - Medical School of Chinese PLA, Beijing, China.
FAU - Wen, Li
AU  - Wen L
AD  - Department of Stomatology, The First Medical Center, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Li, Yun-Xia
AU  - Li YX
AD  - Department of Stomatology, The First Medical Center, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Yang, Shuo
AU  - Yang S
AD  - Department of Stomatology, The First Medical Center, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Zhu, Biao
AU  - Zhu B
AD  - Department of Stomatology, Fuxing Hospital, Capital Medical University, Beijing, 
      China.
FAU - Tian, Xiao-Yu
AU  - Tian XY
AD  - Medical School of Chinese PLA, Beijing, China.
FAU - Li, Shuang
AU  - Li S
AD  - Department of Stomatology, Fuxing Hospital, Capital Medical University, Beijing, 
      China.
FAU - Zhao, Li-Sheng
AU  - Zhao LS
AD  - Department of Stomatology, The First Medical Center, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Dang, Rui-Jie
AU  - Dang RJ
AD  - Department of Stomatology, The First Medical Center, Chinese PLA General 
      Hospital, Beijing, China.
FAU - Jiao, Ting
AU  - Jiao T
AD  - Department of Oncology, Affiliated Hospital of Hebei University, Hebei Key 
      Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, China.
FAU - Zhang, Hai-Song
AU  - Zhang HS
AD  - Department of Oncology, Affiliated Hospital of Hebei University, Hebei Key 
      Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, China.
FAU - Wen, Ning
AU  - Wen N
AD  - Department of Stomatology, The First Medical Center, Chinese PLA General 
      Hospital, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20220228
PL  - Korea (South)
TA  - Int J Stem Cells
JT  - International journal of stem cells
JID - 101497587
PMC - PMC9705154
OTO - NOTNLM
OT  - Cannabidiol (CBD)
OT  - Cannabinoid receptor 2 (CB2)
OT  - Inflammatory microenvironment
OT  - Osteogenic differentiation
OT  - p38 MAPK signaling pathway
COIS- Potential Conflict of Interest The authors have no conflicting financial 
      interest.
EDAT- 2022/02/28 06:00
MHDA- 2022/02/28 06:01
PMCR- 2022/02/28
CRDT- 2022/02/27 20:37
PHST- 2021/09/07 00:00 [received]
PHST- 2021/11/29 00:00 [revised]
PHST- 2022/01/04 00:00 [accepted]
PHST- 2022/02/28 06:00 [pubmed]
PHST- 2022/02/28 06:01 [medline]
PHST- 2022/02/27 20:37 [entrez]
PHST- 2022/02/28 00:00 [pmc-release]
AID - ijsc21152 [pii]
AID - ijsc-15-4-405 [pii]
AID - 10.15283/ijsc21152 [doi]
PST - ppublish
SO  - Int J Stem Cells. 2022 Nov 30;15(4):405-414. doi: 10.15283/ijsc21152. Epub 2022 
      Feb 28.