EMAIL THIS PAGE TO A FRIEND

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

SHP2 regulates osteoclastogenesis by promoting preosteoclast fusion.


PMID 25593124

Abstract

Genes that regulate osteoclast (OC) development and function in both physiologic and disease conditions remain incompletely understood. Shp2 (the Src homology-2 domain containing protein tyrosine phosphatase 2), a ubiquitously expressed cytoplasmic protein tyrosine phosphatase, is implicated in regulating M-CSF and receptor activator of nuclear factor-κB ligand (RANKL)-evoked signaling; its role in osteoclastogenesis and bone homeostasis, however, remains unknown. Using a tissue-specific gene knockout approach, we inactivated Shp2 expression in murine OCs. Shp2 mutant mice are phenotypically osteopetrotic, featuring a marked increase of bone volume (BV)/total volume (TV) (+42.8%), trabeculae number (Tb.N) (+84.1%), structure model index (+119%), and a decrease of trabecular thickness (Tb.Th) (-34.1%) and trabecular spacing (Tb.Sp) (-41.0%). Biochemical analyses demonstrate that Shp2 is required for RANKL-induced formation of giant multinucleated OCs by up-regulating the expression of nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1), a master transcription factor that is indispensable for terminal OC differentiation. Shp2 deletion, however, has minimal effect on M-CSF-dependent survival and proliferation of OC precursors. Instead, its deficiency aborts the fusion of OC precursors and formation of multinucleated OCs and decreases bone matrix resorption. Moreover, pharmacological intervention of Shp2 is sufficient to prevent preosteoclast fusion in vitro. These findings uncover a novel mechanism through which Shp2 regulates osteoclastogenesis by promoting preosteoclast fusion. Shp2 or its signaling partners could potentially serve as pharmacological targets to regulate the population of OCs locally and/or systematically, and thus treat OC-related diseases, such as periprosthetic osteolysis and osteoporosis.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB2700022
Anti-NS1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB2700186
Anti-NS1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB2700193
Anti-NS1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB4300559
Anti-PTPN11 (Ab-542) antibody produced in rabbit, affinity isolated antibody
SAB4300560
Anti-PTPN11 (Ab-580) antibody produced in rabbit, affinity isolated antibody
SAB2900281
Anti-PTPN11 (AB1) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB2900375
Anti-PTPN11 (AB2) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
GW21495A Anti-PTPN11 antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
SAB1406345
Anti-PTPN11 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB4502536
Anti-SH-PTP2 antibody produced in rabbit, affinity isolated antibody
SAB4502534
Anti-SHP-2, C-Terminal antibody produced in rabbit, affinity isolated antibody
SAB4502535
Anti-SHP-2, C-Terminal antibody produced in rabbit, affinity isolated antibody
PRS3901
Anti-SHP2 (ab1) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
PRS3903
Anti-SHP2 (ab2) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB1301000
Anti-SHP2 (Y584) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB1300500
Anti-SHP2 antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
SAB1306770
ANTI-SHP2 antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution