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Melatonin attenuates degenerative disc degression by downregulating DLX5 via the TGF /Smad2/3 pathway in nucleus pulposus cells

Year: 2024

Type: article

Abstract: Background: Intervertebral disc degeneration (IVDD) is the leading cause of low back pain, and apoptosis plays a key role in its pathogenesis. Distal-less homeobox 5 (Dlx5) has been reported to induce cell apoptosis. Melatonin, as a powerful antiapoptotic agent, has been widely reported. Aim: This study aimed to investigate the role of DLX5 in the pathogenesis of IVDD and the potential therapeutic role of melatonin in targeting DLX5 in IVDD. Materials & Methods: Western blotting, RT-qPCR, immunohistochemistry, si-DLX5, Ex-DLX5, flow cytometry, and immunofluorescence were used to examine the regulatory effect of DLX5 on apoptosis. Therapeutic efficacy was assessed by the intraperitoneal injection of melatonin into IVDD mice. Results: The expression level of DLX5 is significantly increased in IVDD, and the expression levels were positively correlated with the grade of IVDD. DLX5 was significantly upregulated in TNF-α-induced degenerative NP cells. Degenerative NP cells transfected with si-DLX5 exhibited significantly less apoptosis than control cells. Melatonin significantly alleviated IVDD in surgically induced IVDD model mice. Discussion: The results revealed that the expression of DLX5 was positively correlated with the severity of IVDD and that melatonin ameliorated DLX5-induced apoptosis and extracellular matrix imbalance by inhibiting the TGF-β/Smad signaling pathway. This study may provide therapeutic strategies to alleviate inflammation-induced apoptosis IVDD-associated inflammation-induced apoptosis. Conclusion: DLX5 plays an important role in IVDD progression by promoting apoptosis, and melatonin represents a promising therapeutic strategy for alleviating IVDD-associated inflammation and apoptosis.

Source: JOR Spine

DOI: 10.1002/jsp2.70014

Authors: Kuibo Zhang, Hua Wang, Ling Mo, Xiaohui Huang, Chao Yuan, Caijun Liu