Abstract
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.
Highlights
Intervertebral disc (IVD) degeneration (IVDD) is a common type of degenerative change in the spine, leading to disc herniation, spinal stenosis, spinal instability, and other degenerative diseases of the spine (Brinjikji et al.Cheng et al Mol Med (2021) 27:922015; Sun et al 2017; Dudli et al 2014; Zhu et al 2017)
This study reveals that Cannabinoid type 2 receptor (CB2) activation can effectively delay the development of IVDD, providing an effective therapeutic target for IVDD
CB2 expression is reduced in degenerated NP tissue As shown in Fig. 1A, we collected normal and degenerated NP tissue from patients and found different levels of IVDD based on the Pfirrmann grade
Summary
Intervertebral disc (IVD) degeneration (IVDD) is a common type of degenerative change in the spine, leading to disc herniation, spinal stenosis, spinal instability, and other degenerative diseases of the spine (Brinjikji et al.Cheng et al Mol Med (2021) 27:922015; Sun et al 2017; Dudli et al 2014; Zhu et al 2017). Intervertebral disc (IVD) degeneration (IVDD) is a common type of degenerative change in the spine, leading to disc herniation, spinal stenosis, spinal instability, and other degenerative diseases of the spine (Brinjikji et al. Cheng et al Mol Med (2021) 27:92. It has been reported that IVDD is a major cause of low back pain (LBP), and more than 70 % of the population has suffered from LBP in their lifetime (Walker 2000; Driscoll et al 2014). Exploring the pathogenesis of IVDD in depth will play a vital role in discovering its potential treatment approaches. 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
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