Abstract
ObjectiveThe aim of this study is to verify whether melatonin (Mel) could mitigate intervertebral disk degeneration (IVDD) in rats and to investigate the potential mechanism of it.MethodA rat acupuncture model of IVDD was established with intraperitoneal injection of Mel. The effect of Mel on IVDD was analyzed via radiologic and histological evaluations. The specific Mel receptors were investigated in both the nucleus pulposus (NP) and cartilaginous endplates (EPs). In vitro, EP cartilaginous cells (EPCs) were treated by different concentrations of Mel under lipopolysaccharide (LPS) and Luzindole conditions. In addition, LPS-induced inflammatory response and matrix degradation following nuclear factor kappa-B (NF-κB) pathway activation were investigated to confirm the potential mechanism of Mel on EPCs.ResultsThe percent disk height index (%DHI) and MRI signal decreased after initial puncture in the degeneration group compared with the control group, while Mel treatment protected disk height from decline and prevented the loss of water during the degeneration process. In the meantime, the histological staining of the Mel groups showed more integrity and well-ordered construction of the NP and EPs in both low and high concentration than that of the degeneration group. In addition, more deep-brown staining of type II collagen (Coll-II) was shown in the Mel groups compared with the degeneration group. Furthermore, in rat samples, immunohistochemical staining showed more positive cells of Mel receptors 1a and 1b in the EPs, instead of in the NP. Moreover, evident osteochondral lacuna formation was observed in rat EPs in the degeneration group; after Mel treatment, the osteochondral destruction alleviated accompanying fewer receptor activator for nuclear factor-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP)-stained positive cells expressed in the EPs. In vitro, Mel could promote the proliferation of EPCs, which protected EPCs from degeneration under LPS treatment. What is more, Mel downregulated the inflammatory response and matrix degradation of EPCs activated by NF-κB pathway through binding to its specific receptors.ConclusionThese results indicate that Mel protects the integrity of the EPs and attenuates IVDD by binding to the Mel receptors in the EPs. It may alleviate the inflammatory response and matrix degradation of EPCs activated by NF-κB pathway.
Highlights
Low back pain (LBP) is a universal health problem
Semiquantification by MRI grade showed that MRI scores in both the low- and high-concentration Mel groups were significantly lower than in the degeneration group at 7 days (Figure 1C). These results indicated that Mel treatment alleviated punctureinduced IVDD in rats
The results of this study demonstrated that exogenous Mel protects EP chondrocytes (EPCs) from degeneration through decreasing inflammatory response and degradation of ECM induced by NF-κB pathway after binding to its specific receptors in vitro and exerts an alleviative effect on IVDD by protecting the EPs and its subchondral bones from damage in vivo
Summary
Low back pain (LBP) is a universal health problem. LBP causes both tremendous psychological and financial burdens for patients, families, and society as a whole (Hong et al, 2013). The most common cause of LBP is intervertebral disk (IVD) degeneration (IVDD) (Luoma et al, 2000). The pathogenesis of IVDD is complicated and includes oxidative stress, inflammatory response, and apoptosis. Most studies focus on the pathological change of the nucleus pulposus (NP). Few studies have examined the relationship between cartilaginous endplates (EPs) and IVDD. Several methods, such as physical exercise, medical intervention, surgical treatment, and gene therapy are used to treat IVDD, none of them can effectively restore degenerated disks (Sakai et al, 2005)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
