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The role of cannabinoid type 2 receptor in mediating osteogenic differentiation induced by hypoxia in rat bone mesenchymal stem cells |
HU Xuzhi, SHI Xinlian, DENG Hui |
Department of Periodontics, Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China |
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Cite this article: |
HU Xuzhi,SHI Xinlian,DENG Hui. The role of cannabinoid type 2 receptor in mediating osteogenic differentiation induced by hypoxia in rat bone mesenchymal stem cells[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2019, 49(8): 563-567.
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Abstract Objective: To explore whether cannabinoid type 2 receptor (CB2) participates in the regulation of BMSCs osteogenic differentiation and how it is regulated by hypoxic microenvironment. Methods: The whole bone marrow cell adherence method was used to isolate and culture rBMSCs. Low-oxygen model was established by using different concentrations of chemical oxygen peroxide cobalt chloride (CoCl2). Real-time PCR and Western blotting were used to detect the expression of osteogenesis key proteins RUNX2 and OCN at the gene and protein levels. Further, combined with the CB2 inhibitor AM630, the role of CB2 in the osteogenic differentiation of rBMSCs in a hypoxic microenvironment was investigated. Results: Compared with the control group, the expression of RUNX2 and OCN mRNA and protein in rBMSCs increased significantly at 24, 48, 72, 96 h after hypoxia treatment (P<0.05); Oxygen treatment up-regulated mRNA and protein expression of CB2 (P<0.05). CB2 inhibitor AM630 inhibited the expression of RUNX2 and OCN induced by hypoxia (P<0.05). Conclusion: CB2 is involved in the regulation of osteogenic differentiation of rBMSCs promoted by hypoxia.
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[1] PRADEEP A R, PRAPULLA D V, SHARMA A, et al. Gingival crevicular fluid and serum vascular endothelial growth factor: their relationship in periodontal health, disease and after treatment[J]. Cytokine, 2011, 54(2): 200-204.
[2] NG K T, LI J P, NG K M, et al. Expression of hypoxia-inducible factor-1α in human periodontal tissue[J]. J Periodontol, 2011, 82(1): 136-141.
[3] TAKEDACHI M, IYAMA M, SAWADA K, et al. Hypoxia-inducible factor-1α inhibits interleukin-6 and -8 production in gingival epithelial cells during hypoxia[J]. J Periodontal Res, 2017, 52(1): 127-34.
[4] 史新连, 胡碧波, 任曼曼, 等. 低氧调控大鼠骨髓间充质干细胞OPG/RANKL mRNA的表达[J]. 上海口腔医学, 2017, 26(3): 258-262.
[5] KARSAK M, COHEN-SOLAL M, FREUDENBERG J, et al. Cannabinoid receptor type 2 gene is associated with human osteoporosis[J]. Hum Mol Genet, 2005, 14(22): 3389-3396.
[6] OFEK O, KARSAK M, LECLERC N, et al. Peripheral cannabinoid receptor, CB2, regulates bone mass[J]. Proc Natl Acad Sci U S A, 2006, 103(3): 696-701.
[7] SUN Y X, XU A H, YANG Y, et al. Activation of cannabinoid receptor 2 enhances osteogenic differentiation of bone marrow derived mesenchymal stem cells[J]. Biomed Res Int, 2015, 2015: 874982.
[8] QIAN H, ZHAO Y, PENG Y, et al. Activation of cannabinoid receptor CB2 regulatesosteogenic and osteoclastogenic gene expression in human periodontal ligament cells[J]. J Periodontal Res, 2010, 45(4): 504-511.
[9] TANAKA M, HANIOKA T, TAKAYA K, et al. Association of oxygen tension in human periodontal pockets with gingival inflammation[J]. J Periodontol, 1998, 69(10): 1127-1130.
[10] 赵剑锋, 傅惠英, 吕伯东. 低氧细胞模型的研究进展[J]. 解剖学杂志, 2014, 37(2): 261-263.
[11] WAGEGG M, GABER T, LOHANATHA F L, et al. Hypoxia promotes osteogenesis but suppresses adipogenesis of human mesenchymal stromal cells in a hypoxia-inducible factor-1 dependent manner[J]. PLoS One, 2012, 7(9): e46483.
[12] ZOU D, HAN W, YOU S, et al. In vitro study of enhanced osteogenesis induced by HIF-1α-transduced bone marrow stem cells[J]. Cell Prolif, 2011, 44(3): 234-243.
[13] HSU S H, CHEN C T, WEI Y H. Inhibitory effects of hypoxia on metabolic switch and osteogenic differentiation of human mesenchymal stem cells[J]. Stem Cells, 2013, 31(12): 2779-2788.
[14] LI Y, KIM J. Neuronal expression of CB2 cannabinoid receptor mRNAs in the mouse hippocampus[J]. Neuroscience, 2015, 311: 253-267.
[15] BAB I, ZIMMER A, MELAMED E. Cannabinoids and the skeleton: from marijuana to reversal of bone loss[J]. Ann Med, 2009, 41(8): 560-567.
[16] IDRIS A I, SOPHOCLEOUS A, LANDAO-BASSONGA E, et al. Regulation of bone mass, osteoclast function, and ovariectomy-induced bone loss by the type 2 cannabinoid receptor[J]. Endocrinology, 2008, 149(11): 5619-5626.
[17] SOPHOCLEOUS A, MARINO S, KABIR D, et al. Combined deficiency of the Cnr1 and Cnr2 receptors protects against age-related bone loss by osteoclast inhibition[J].Aging Cell, 2017, 16(5): 1051-1061.
[18] ROSSI F, BELLINI G, TORTORA C, et al. CB(2) and TRPV(1) receptors oppositely modulate in vitro human osteoblast activity[J]. Pharmacol Res, 2015, 99: 194-201. |
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