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TRP14 attenuates osteoclast differentiation by inhibiting NF‐κB and MAPK signaling
Author(s) -
Hong Sohyun,
Kim Hojin,
Jeong Woojin
Publication year - 2010
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.24.1_supplement.lb170
Subject(s) - rankl , osteoclast , p38 mitogen activated protein kinases , microbiology and biotechnology , chemistry , mapk/erk pathway , kinase , nf κb , activator (genetics) , phosphorylation , bone resorption , rank ligand , signal transduction , receptor , biochemistry , biology , endocrinology
TRP14 is a disulfide reductase containing the CXXC motif which regulates NF‐κB and mitogen‐activated protein kinases (MAPKs) stimulated by TNFα. Given that NF‐κB and MAPK signaling play an important role in osteoclastogenesis, it was examined whether TRP14 can inhibit osteoclast differentiation. Osteoclast differentiation of RAW264.7 macrophages by receptor activator of NF‐κB ligand (RANKL) was enhanced by depletion of TRP14, while it was inhibited by TRP14 overexpression, as revealed by tartrate‐resistant acid phosphatase (TRAP) staining and TRAP activity assay. When RAW264.7 cells was exposed to RANKL, depletion of TRP14 augmented phosphorylation and degradation of IκBα, and activation of c‐Jun NH 2 ‐terminal kinase (JNK) and p38 as well as consequent induction of nuclear factor of activated T cell, cytoplasmic 1 (NFATc1) that is a pivotal determinant of osteoclastogenesis. In addition depletion of TRP14 strongly expanded actin ring formation that is a prerequisite for osteoclast bone resorption, and significantly increased RANKL‐mediated ROS production. Taken together TRP14 attenuates osteoclast differentiation by inhibiting NF‐κB, JNK and p38 activated by RANKL.