ERα signaling regulates MMP3 expression to induce FasL cleavage and osteoclast apoptosis.

ABSTRACT: The benefits of estrogens on bone health are well established; how estrogens signal to regulate bone formation and resorption is less well understood. We show here that 17β-estradiol (E2)-induced apoptosis of bone-resorbing osteoclasts is mediated by cleavage and solubilization of osteoblast-expressed Fas ligand (FasL). U2OS-ERα osteoblast-like cells expressing an EGFP-tagged FasL at the C-terminus showed decreased fluorescence after E2 treatment, indicative of a cleavage event. Treatment of U2OS-ERα cultures with a specific MMP3 inhibitor in the presence of E2 blocked FasL cleavage and showed an increase in the number of EGFP-FasL+ cells. siRNA experiments successfully knocked down MMP3 expression and restored full-length FasL to basal levels. E2 treatment of both human and murine primary

SUBMITTER: Garcia AJ 

PROVIDER: S-EPMC3524410 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature