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Thrombin induces cyclooxygenase‐2 expression through MAPKs and NF‐¿B in osteoblast MC3T3‐E1 cells
Author(s) -
Chiang YiChen,
Hsieh HsiLung,
Yang ChuenMao
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.570.6
Subject(s) - thrombin , p38 mitogen activated protein kinases , osteoblast , mapk/erk pathway , chemistry , microbiology and biotechnology , kinase , phosphorylation , biochemistry , medicine , biology , platelet , in vitro
Thrombin, a serine protease, has hormone‐like effects on cells from many tissues, including bone. Thrombin can induce expression of COX‐2 catalyzed the synthesis of prostaglandin (PG) in osteoblasts, which plays a crucial role in regulating bone resorption. Here, the mechanisms of MAPKs and NF‐κB pathways involved in thrombin‐induced COX‐2 expression were investigated in MC3T3‐E1 osteoblast cells. In this study, we demonstrated that thrombin‐induced COX‐2 protein and mRNA expression in a time‐ and concentration‐dependent manner, which was attenuated by pharmacological inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125) and NF‐κB (Bay11‐7082), revealed by RT‐PCR and Western blot analyses. Consistently, thrombin‐stimulated phosphorylation of p42/p44 MAPK, p38 MAPK and JNK1/2 was attenuated by pretreatment with U0126, SB202190 or SP600125. The implication of NF‐κB in thrombin‐mediated responses was supported by translocation of NF‐κB into the nucleus and degradation of IκB‐α stimulated by thrombin. Taken together, these results suggest that in MC3T3‐E1 osteoblast cells, activation of MAPKs and NF‐κB translocation are essential for thrombin‐induced COX‐2 gene expression. These results provide new insight into the mechanisms by which thrombin may contribute to bone remodeling.