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Fluocinolone acetonide partially restores the mineralization of LPS‐stimulated dental pulp cells through inhibition of NF‐κB pathway and activation of AP ‐1 pathway
Author(s) -
Liu Zhongning,
Jiang Ting,
Wang Xinzhi,
Wang Yixiang
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12404
Subject(s) - osteocalcin , western blot , chemistry , dentin sialophosphoprotein , microbiology and biotechnology , inflammation , immunostaining , alkaline phosphatase , nf κb , proinflammatory cytokine , pharmacology , signal transduction , medicine , biology , biochemistry , immunohistochemistry , gene , enzyme
Background and Purpose 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. Experimental Approach 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. Key Results 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 P 65 and activating activator protein‐1 ( AP ‐1) (p‐c‐ J un and F ra‐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. Conclusions and Implications 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.