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.
Pulpitis/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction ; Humans ; Mice ; Mice, Knockout ; Dental Pulp/metabolism* ; Disease Models, Animal ; Lipopolysaccharides

Objective To analyze the correlation between different types of anemia(small cell anemia and nor-mal cell anemia)before operation and pathological features and prognosis of colorectal cancer patients.Methods The clinical data of 130 patients with colorectal cancer who underwent radical surgery in our hospital from March 2018 to February 2021 were retrospectively analyzed.According to the morphology of red blood cells,the patients were divided into group A(70 cases without anemia),group B(18 cases with small cell anemia)and group C(42 cases with normal cell anemia).Pathological features and postoperative 2 a survival rate of the 3 groups were compared.The correlation between preoperative anemia types and pathological features of colorectal cancer was analyzed by Phi coefficient test,and Kaplan-Meier survival curve was drawn to compare the survival rate of the 3 groups.Results There were significant differences in gender,tumor site,tumor diameter and TNM stage distribution among the three groups(P<0.05).The Phi coefficient test showed that preoperative anemia type was correlated with gender,tumor site,tumor diameter,and TNM stage(r = 0.238,0.255,0.266,0.331,P = 0.025,0.015,0.010,0.001).Multivariate Logistic regression analysis showed that tumor diameter≥5 cm,TNM stage Ⅲ-Ⅳ,distant metastasis,lymph node metastasis,preoperative small cell anemia,preoperative normal cell anemia were the risk factors for the prognosis of colorectal cancer after radical surgery(OR>1,P<0.05).The overall survival rate of 2a in group A was higher than that in group C>that in group B(P<0.05).Log-rank test showed that the postoperative survival rate of the three groups was significantly different(P<0.05).Conclusion Preoperative anemia types were correlated with tumor site,tumor diameter,TNM stage and postoperative survival time of colorectal cancer patients,among which preoperative small-cell anemia patients had the lowest survival rate.