Pulpitis is a common infective oral disease in clinical situations. The regulatory mechanisms of immune defense in pulpitis are still being investigated. Osteomodulin (OMD) is a small leucine-rich proteoglycan family member distributed in bones and teeth. It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells (hDPSCs). In this study, the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated. The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining. Intriguingly, the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens. The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide (LPS)-induced inflammation. A conditional Omd knockout mouse model with pulpal inflammation was established. LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice, whereas OMD administration exhibited a protective effect against pulpitis. Mechanistically, the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB (NF-κB) signaling pathway. Interleukin-1 receptor 1 (IL1R1), a vital membrane receptor activating the NF-κB pathway, was significantly downregulated in OMD-overexpressing hDPSCs. Additionally, the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking. In vivo, excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist. Overall, OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway. OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.

© 2025. The Author(s).

牙髓炎是临床环境中常见的感染性口腔疾病。牙髓炎免疫防御的调节机制仍在研究中。骨模蛋白（Osteomodulin，OMD）是一种小的富含亮氨酸的蛋白聚糖家族成员，在骨骼和牙齿中均有分布。它是一种生物活性蛋白质，能够促进成骨作用并抑制人源牙髓干细胞（hDPSCs）的凋亡。在这项研究中，我们探讨了OMD在牙髓炎中的作用及其诱导的调节机制。通过免疫荧光染色检测正常和炎症的人类牙髓组织中OMD的表达情况。令人惊讶的是，在牙髓炎样本的炎症浸润区域，OMD的表达量降低。细胞实验表明，重组人源OMD可以抵抗脂多糖（LPS）诱导的炎症有害影响。我们建立了一种条件性Omd敲除小鼠模型以模拟牙髓炎情况。结果显示，在条件性Omd敲除小鼠中，由LPS诱导的炎症损伤显著增加，而给予OMD则表现出对牙髓炎的保护作用。从机制上看，OMD过表达的转录组变化在核因子-κB（NF-κB）信号通路中具有显著富集。白细胞介素-1受体1（IL1R1），一种激活NF-κB途径的重要膜受体，在OMD过表达的人牙髓干细胞中的表达量显著降低。此外，通过共免疫沉淀和分子对接验证了OMD与IL1R1之间的相互作用。在体内实验中，使用IL1受体拮抗剂可以缓解Omd缺陷小鼠的过度牙髓炎症。总体而言，OMD通过IL1R1/NF-κB信号通路在炎性反应中发挥保护作用。OMD可能优化hDPSCs的免疫调节功能，并可用于再生根管治疗。

© 2025. The Author(s).