Intervertebral disc (IVD) degeneration is the primary cause for low back pain that has a high prevalence in modern society and poses enormous economic burden on patients. Few effective therapeutic strategies are available for IVD degeneration treatment. To understand the biological effects of dental pulp stem cells (DPSCs) on nucleus pulposus (NP) cells, we carried out RNA sequencing, bioinformatic analysis which unveiled gene expression differences, and pathway variation in primarily isolated patients’ NP cells after treatment with DPSCs supernatant. Western blot and immunofluorescence were used to verify these molecular alterations. Besides, to evaluate the therapeutic effect of DPSCs in IVD degeneration treatment, DPSCs were injected into a degeneration rat model in situ, with treatment outcome measured by micro-CT and histological analysis. RNA sequencing and in vitro experiments demonstrated that DPSCs supernatant could downregulate NP cells’ inflammation-related NF-κB and JAK-STAT pathways, reduce IL-6 production, increase collagen II expression, and mitigate apoptosis. In vivo results showed that DPSCs treatment protected the integrity of the disc structure, alleviated extracellular matrix degradation, and increased collagen fiber expression. In this study, we verified the therapeutic effect of DPSCs in an IVD degeneration rat model and elucidated the underlying molecular mechanism of DPSCs treatment, which provides a foundation for the application of DPSCs in IVD degeneration treatment.

中文翻译：

---

DPSCs 通过调节髓核免疫状态来保护结构完整性并减轻椎间盘退变

椎间盘（IVD）退变是导致腰痛的主要原因，在现代社会中发病率很高，给患者带来了巨大的经济负担。很少有有效的治疗策略可用于 IVD 变性治疗。为了了解牙髓干细胞 (DPSCs) 对髓核 (NP) 细胞的生物学作用，我们进行了 RNA 测序、生物信息学分析，揭示了用 DPSCs 上清液处理后初步分离的患者的 NP 细胞的基因表达差异和通路变异. 蛋白质印迹和免疫荧光用于验证这些分子改变。此外，为了评估 DPSCs 在 IVD 变性治疗中的治疗效果，将 DPSCs 原位注射到变性大鼠模型中，通过显微 CT 和组织学分析测量治疗结果。κ B 和 JAK-STAT 通路，减少 IL-6 的产生，增加胶原蛋白 II 的表达，并减轻细胞凋亡。体内结果表明，DPSCs 处理保护了椎间盘结构的完整性，减轻了细胞外基质的降解，并增加了胶原纤维的表达。本研究验证了DPSCs在IVD变性大鼠模型中的治疗作用，阐明了DPSCs治疗的潜在分子机制，为DPSCs在IVD变性治疗中的应用奠定了基础。