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Abstract：
Previously we have demonstrated that sclerostin inhibits stress-induced odontogenic differentiation of odontoblasts and accelerates senescence of dental pulp cells (DPCs) Odontoblasts and DPCs are main functioning cells for inflammation resistance and tissue regeneration in dentine-pulp complex. Sclerostin is relevant for systemic inflammation and chronic periodontitis processes, but its effects on dental pulp inflammation remains unclear. In this study, we found that sclerostin expression of odontoblasts was elevated in lipopolysaccharide-induced inflammatory environment, and exogenous sclerostin increased the production of pro-inflammatory cytokines in inflamed odontoblasts. Furthermore, sclerostin activated the NF-κB signaling pathway in inflamed odontoblasts and the NF-κB inhibitor reversed the exaggerative effects of sclerostin on the pro-inflammatory cytokines production. Additionally, sclerostin promoted adhesion and migration of inflamed DPCs, while inhibiting odontoblastic differentiation of inflamed DPCs. Sclerostin also might enhance pulpal angiogenesis. Taken together, it can therefore be inferred that sclerostin is upregulated in inflamed odontoblasts under pulpal inflammatory condition to enhance inflammatory responses in dentine-pulp complex and impair reparative dentinogenesis. This indicates that sclerostin inhibition might be a therapeutic target for anti-inflammation and pro-regeneration during dental pulp inflammation.
摘要：
以前，我们已经证明硬化蛋白抑制应激诱导的成牙本质细胞的成牙分化并加速牙髓细胞（DPCs）的衰老。成牙本质细胞和DPCs是牙本质-牙髓复合物中炎症抗性和组织再生的主要功能细胞。硬化蛋白与全身性炎症和慢性牙周炎过程有关，但其对牙髓炎症的影响尚不清楚。在这项研究中,我们发现，在脂多糖诱导的炎症环境中，成牙本质细胞的硬化蛋白表达升高，和外源性硬化蛋白增加了炎症成牙本质细胞中促炎细胞因子的产生。此外，硬化蛋白激活了炎症成牙本质细胞的NF-κB信号通路，NF-κB抑制剂逆转了硬化蛋白对促炎细胞因子产生的夸大作用。此外,硬化蛋白促进发炎的DPC的粘附和迁移，同时抑制发炎的DPC的成牙本质分化。硬化蛋白还可能增强牙髓血管生成。一起来看,因此，可以推断，在牙髓炎症条件下，硬化蛋白在发炎的成牙本质细胞中上调，以增强牙本质-牙髓复合物中的炎症反应并损害修复性牙本质生成。这表明硬化蛋白抑制可能是牙髓炎症期间的抗炎和促再生的治疗靶标。
