Liu Zhongning, Jiang Ting, Wang Xinzhi, Wang Yixiang
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
Br J Pharmacol. 2013 Nov;170(6):1262-71. doi: 10.1111/bph.12404.
Fluocinolone acetonide (FA) is commonly used as a steroidal anti-inflammatory drug. We recently found that in dental pulp cells (DPCs) FA has osteo-/odonto-inductive as well as anti-inflammatory effects. However, the mechanism by which FA induces these effects in DPCs is poorly understood.
The effect of FA on the mineralization of DPCs during inflammatory conditions and the underlying mechanism were investigated by real-time PCR, Western blot, EMSA, histochemical staining, immunostaining and pathway blockade assays.
FA significantly inhibited the inflammatory response in LPS-treated DPCs not only by down-regulating the expression of pro-inflammation-related genes, but also by up-regulating the expression of the anti-inflammatory gene PPAR-γ and mineralization-related genes. Moreover, histochemical staining and immunostaining showed that FA could partially restore the expressions of alkaline phosphatase, osteocalcin and dentin sialophosphoprotein (DSPP) and mineralization in LPS-stimulated DPCs. Real-time PCR and Western blot analysis revealed that FA up-regulated DSPP and runt-related transcription factor 2 expression by inhibiting the expression of phosphorylated-NF-κB P65 and activating activator protein-1 (AP-1) (p-c-Jun and Fra-1). These results were further confirmed through EMSA, by detection of NF-κB DNA-binding activity and pathway blockade assays using a NF-κB pathway inhibitor, AP-1 pathway inhibitor and glucocorticoid receptor antagonist.
Inflammation induced by LPS suppresses the mineralization process in DPCs. FA partially restored this osteo-/odonto-genesis process in LPS-treated DPCs and had an anti-inflammatory effect through inhibition of the NF-κB pathway and activation of the AP-1 pathway. Hence, FA is a potential new treatment for inflammation-associated bone/teeth diseases.
醋酸氟轻松（FA）是一种常用的甾体类抗炎药。我们最近发现，在牙髓细胞（DPCs）中，FA具有骨/牙本质诱导作用以及抗炎作用。然而，FA在DPCs中诱导这些作用的机制尚不清楚。
通过实时定量PCR、蛋白质免疫印迹法、电泳迁移率变动分析、组织化学染色、免疫染色和通路阻断实验，研究FA在炎症条件下对DPCs矿化的影响及其潜在机制。
FA不仅通过下调促炎相关基因的表达，还通过上调抗炎基因PPAR-γ和矿化相关基因的表达，显著抑制LPS处理的DPCs中的炎症反应。此外，组织化学染色和免疫染色显示，FA可部分恢复LPS刺激的DPCs中碱性磷酸酶、骨钙素和牙本质涎磷蛋白（DSPP）的表达以及矿化。实时定量PCR和蛋白质免疫印迹分析表明，FA通过抑制磷酸化-NF-κB P65的表达并激活活化蛋白-1（AP-1）（p-c-Jun和Fra-1）来上调DSPP和 runt相关转录因子2的表达。通过电泳迁移率变动分析检测NF-κB DNA结合活性，以及使用NF-κB通路抑制剂、AP-1通路抑制剂和糖皮质激素受体拮抗剂进行通路阻断实验，进一步证实了这些结果。
LPS诱导炎症抑制DPCs中的矿化过程。FA可部分恢复LPS处理的DPCs中的这种骨/牙本质生成过程，并通过抑制NF-κB通路和激活AP-1通路发挥抗炎作用。因此，FA是一种治疗炎症相关骨/牙疾病的潜在新疗法。
