Fu Song, Lv Renhua, Wang Longqiang, Wang Zhenyu, Wang Fengming, Gao Hao, Zhao Wei, Huang Xiaoling, Li Xiaojun, Wang Yanan
Department of Minimally Invasive Spine Surgery, Shandong Wendeng Orthopedic Hospital, No.1, Fengshan Road, Wendeng District, Weihai, 264400, Shandong Province, China.
Department of Neurology, Weihai Central Hospital, Weihai, Shandong Province, China.
Sci Rep. 2025 May 2;15(1):15378. doi: 10.1038/s41598-025-00278-x.
Intervertebral disc degeneration (IVDD) and its attendant lower back pain are a major medical challenge. Ferroptosis has become a new target for the treatment of IVDD. Mesenchymal stem cells (MSCs) are a promising regenerative therapy for IVDD. Hydrogel is usually used as a delivery carrier for MSCs. This study investigated the effect of bone mesenchymal stem cells (BMSCs) in IVDD by magnetic resonance imaging (MRI) and hematoxylin and eosin (HE) staining analysis using a rat-punctured IVDD model. A vitro model of tert-butyl hydroperoxide (TBHP)-induced oxidative stress injury in annulus fibrosus cells (AFCs) was used to explore the underlying molecular mechanisms. Cell viability was detected by cell counting kit-8 assay. Ferroptosis was assessed by measuring the levels of LDH, Fe, glutathione, lipid reactive oxygen species, and malondialdehyde. The underlying mechanism was investigated by western blot and phosphor-kinase array. Results suggested that BMSCs inhibited TBHP-induced ferroptosis and the phosphorylated levels of STAT3 in AFCs. The activation of STAT3 (colivelin, a specific agonist for STAT3) reversed the effects on the ferroptosis of BMSCs. Additionally, BMSCs alleviated IVDD progression based on matrix hydrogels, while colivelin abolished the protective effects of BMSCs-encapsulated hydrogels on IVDD. In short, BMSCs inhibited oxidative stress-induced AFCs ferroptosis, thereby alleviating IVDD, which is associated with inhibited STAT3 activation. This study demonstrated the possible underlying mechanism by which BMSCs mitigate IVDD and may provide a new therapeutic idea for IVDD.
椎间盘退变（IVDD）及其伴随的下背部疼痛是一项重大的医学挑战。铁死亡已成为治疗IVDD的新靶点。间充质干细胞（MSCs）是一种有前景的IVDD再生疗法。水凝胶通常用作MSCs的递送载体。本研究使用大鼠穿刺IVDD模型，通过磁共振成像（MRI）和苏木精-伊红（HE）染色分析，研究了骨间充质干细胞（BMSCs）对IVDD的影响。使用叔丁基过氧化氢（TBHP）诱导的纤维环细胞（AFCs）氧化应激损伤的体外模型，探讨其潜在的分子机制。通过细胞计数试剂盒-8检测细胞活力。通过测量乳酸脱氢酶、铁、谷胱甘肽、脂质活性氧和丙二醛的水平评估铁死亡。通过蛋白质免疫印迹和磷酸激酶阵列研究潜在机制。结果表明，BMSCs抑制TBHP诱导的AFCs铁死亡和STAT3的磷酸化水平。STAT3的激活剂（colivelin，一种STAT3特异性激动剂）逆转了对BMSCs铁死亡的影响。此外，基于基质水凝胶，BMSCs减轻了IVDD的进展，而colivelin消除了封装BMSCs的水凝胶对IVDD的保护作用。简而言之，BMSCs抑制氧化应激诱导的AFCs铁死亡，从而减轻IVDD，这与抑制STAT3激活有关。本研究证明了BMSCs减轻IVDD的可能潜在机制，并可能为IVDD提供新的治疗思路。
