SH3BP2 is an activator of NFAT activity and osteoclastogenesis.
SH3BP2 is an activator of NFAT activity and osteoclastogenesis.
复制标题
DOI：
10.1016/j.bbrc.2008.04.080
复制
发表时间：
2008-07
影响因子：
3.1
通讯作者：
S. Lietman;L. Yin;M. Levine
中科院分区：
文献类型：
--
作者：
S. Lietman;L. Yin;M. Levine
Heterozygous activating mutations in exon 9 of SH3BP2 have been found in most patients with cherubism, an unusual genetic syndrome characterized by excessive remodeling of the mandible and maxilla due to spontaneous and excessive osteoclastic bone resorption. Osteoclasts differentiate after binding of sRANKL to RANK induces a number of downstream signaling effects, including activation of the calcineurin/NFAT (nuclear factor of activated T cells) pathway. Here, we have investigated the functional significance of SH3BP2 protein on osteoclastogenesis in the presence of sRANKL. Our results indicate that SH3BP2 both increases nuclear NFATc1 in sRANKL treated RAW 264.7 preosteoclast cells and enhances expression of tartrate resistant acid phosphatase (TRAP), a specific marker of osteoclast differentiation. Moreover, overexpression of SH3BP2 in RAW 264.7 cells potentiates sRANKL-stimulated phosphorylation of PLCγ1 and 2, thus providing a mechanistic pathway for the rapid translocation of NFATc1 into the nucleus and increased osteoclastogenesis in cherubism.
