Premium
The adaptor protein 3BP2/SH3BP2 is required for RANKL‐induced osteoclastogenesis in RAW264.7 cells
Author(s) -
Guezguez Amel,
Mouska Xavier,
BlinWakkach Claudine,
Breittmayer JeanPhilippe,
Simoncic Paul D.,
Rottapel Robert,
Deckert Marcel
Publication year - 2008
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.22.1_supplement.1051.2
Subject(s) - rankl , microbiology and biotechnology , signal transducing adaptor protein , osteoclast , signal transduction , junb , biology , p38 mitogen activated protein kinases , syk , cancer research , mapk/erk pathway , transcription factor , activator (genetics) , tyrosine kinase , receptor , gene , biochemistry
The adaptor protein (Abl SH3 binding protein‐2), a partner of Src and Syk kinases families, has been involved in leukocyte signaling and activation. Recently, genetic studies have associated mutations of 3BP2 gene with the human bone disease cherubism and with inflammation and bone dysfunction in mouse. Here the role of 3BP2 in osteoclast differentiation was investigated. Using stable extinction of 3BP2 expression in the RAW264.7 monocyte/macrophage cell line, we show that 3BP2 is required for RANKL‐induced differentiation of RAW264.7 cells into multinucleated TRAP+ osteoclasts, but not for GM‐CSF/IL4‐induced differentiation into dendritic cells. The absence of 3BP2 in RAW264.7 cells is associated with reduced actin cytoskeleton organization and impaired RANKL‐induced cell motility and fusion, and activation of IKK, ERK, JNK, but not of p38. In addition, we found a dramatic decrease of NFATc1, AP‐1 and NFkB transcription factors activities induced by RANKL stimulation, as well as a deregulated expression of multiple genes involved in early events controlling osteoclastogenesis, including NFATc1, c‐fos, beta3 integrin subunit, and several chemokine and chemoreceptor genes. Together, these data define the adaptor protein as a critical effector of multiple RANKL‐dependent signal transduction pathways involved in osteoclast differentiation. This work was supported by INSERM and ANR‐MRAR.