CB2-mediated attenuation of nucleus pulposus degeneration via the amelioration of inflammation and oxidative stress in vivo and in vitro

Molecular Medicine

Zhanghuan Chen¹  Jiacheng Du¹  Zhongchen Dong¹  Feng Zhou¹  Xiexin Wu¹  Dechun Geng¹  Jiayi Lin¹  Congxin Xu¹  Huilin Yang¹  Yubo Mao¹  Xiaoqiang Cheng² 

[1] Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188, Shi Zi Road, 215006, Suzhou, China;Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188, Shi Zi Road, 215006, Suzhou, China;Department of Orthopaedics, Nanjing First Hospital, Nanjing Medical University, 210000, Nanjing, China;

关键词: Intervertebral disc degeneration;    Nucleus pulposus cell;    Inflammation;    Oxidative stress;    Cannabinoid type 2 receptor;   

DOI  :  10.1186/s10020-021-00351-x

来源: Springer

【 摘 要 】

BackgroundNucleus pulposus cell (NPC) degeneration is widely accepted as one of the major causes of intervertebral disc (IVD) degeneration (IVDD). The pathogenesis of IVDD is complex and consists of inflammation, oxidative stress, and the loss of extracellular matrix (ECM). Cannabinoid type 2 receptor (CB2) has been shown to be involved in the pathological mechanism of a variety of diseases due to its anti-inflammatory effects and antioxidative stress capacity.MethodIn Vitro, H2O2 was used to induce degeneration of nucleus pulposus cells, mRNA and protein expression level was determined by RT-PCR and Western Blot, and Immunocytochemical staining were used to detect expression of collagen II, aggrecan, MMP3/13, superoxide dismutase 2 (SOD2) and inducible nitric oxide synthase (iNOS). In vivo, the potential therapeutic effect of CB2 was detected in the rat acupuncture model.ResultIn vitro, we found that the CB2 agonist (JWH133) treatment reduced the oxidative stress level in NPCs induced by hydrogen peroxide (H2O2) treatment. Furthermore, the expression of inflammatory cytokines was also decreased by JWH133 treatment. We found that collagen II and aggrecan expression was preserved, whereas matrix metalloproteinase levels were reduced. In vivo, we established a rat model by needle puncture. Imaging assessment revealed that the disc height index (DHI) and morphology of IVD were significantly improved, and the disc degeneration process was delayed by treatment of JWH133. Furthermore, immunohistochemical (IHC) staining revealed that JWH133 could inhibit the degradation of collagen II and decrease the expression of MMP3.ConclusionsThe experiment indicates the oxidative stress and inflammatory response of rat NPCs induced by H2O2 could be inhibited by activating CB2. This study reveals that CB2 activation can effectively delay the development of IVDD, providing an effective therapeutic target for IVDD.

【 授权许可】

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