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

被引:19
作者
Cheng, Xiaoqiang [1 ,2 ]
Lin, Jiayi [1 ]
Chen, Zhanghuan [1 ]
Mao, Yubo [1 ]
Wu, Xiexin [1 ]
Xu, Congxin [1 ]
Du, Jiacheng [1 ]
Dong, Zhongchen [1 ]
Yang, Huilin [1 ]
Zhou, Feng [1 ]
Geng, Dechun [1 ]
机构
[1] Soochow Univ, Dept Orthopaed, Affiliated Hosp 1, 188 Shi Zi Rd, Suzhou 215006, Peoples R China
[2] Nanjing Med Univ, Nanjing Hosp 1, Dept Orthopaed, Nanjing 210000, Peoples R China
基金
中国国家自然科学基金;
关键词
Intervertebral disc degeneration; Nucleus pulposus cell; Inflammation; Oxidative stress; Cannabinoid type 2 receptor; INTERVERTEBRAL DISC DEGENERATION; LOW-BACK-PAIN; APOPTOSIS; PREVENTS; PUNCTURE; NEEDLE; CELLS; MODEL;
D O I
10.1186/s10020-021-00351-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background Nucleus 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. Method In 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. Result In 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. Conclusions The 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.
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