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CHIP regulates skeletal development and postnatal bone growth
Author(s) -
Wang Wenbo,
Li Jun,
Ko Frank C.,
Zhao Xia,
Qiao Yusen,
Lu Ronald S.,
Sumner D. Rick,
Wang Tingyu,
Chen Di
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29424
Subject(s) - ubiquitin ligase , osteoclast , conditional gene knockout , microbiology and biotechnology , ubiquitin , transcription factor , organ on a chip , osteoblast , biology , chemistry , receptor , endocrinology , biochemistry , materials science , gene , nanotechnology , phenotype , microfluidics , in vitro
C terminus of Hsc70‐interacting protein (CHIP) is a chaperone‐dependent and U‐box containing E3 ubiquitin ligase. In previous studies, we found that CHIP regulates the stability of multiple tumor necrosis factor receptor‐associated factor proteins in bone cells. In Chip global knockout (KO) mice, nuclear factor‐κB signaling is activated, osteoclast formation is increased, osteoblast differentiation is inhibited, and bone mass is decreased in postnatal Chip KO mice. To determine the role of Chip in different cell types at different developmental stages, we created Chip flox/flox mice. We then generated Chip conditional KO mice Chip CMV and Chip OsxER and demonstrated defects in skeletal development and postnatal bone growth in Chip conditional KO mice. Our findings indicate that Chip conditional KO mice could serve as a critical reagent for further investigations of functions of CHIP in bone cells and in other cell types.