Novel role of Suppressor of Cytokine Signaling 3 in regulating LPS‐induced Matrix Metalloproteinase 13 gene expression in osteoblasts

Abstract

Suppressors of cytokine signaling 3 (SOCS3) is a key regulator of cytokine signaling in macrophages and T cells. Although SOCS3 seems to contribute to the balance between the pro‐inflammatory effects of IL‐6 family of cytokines and anti‐inflammatory signaling of IL‐10 by regulating gp130/Jak/Stat3 signal transduction, how SOCS3 controls the downstream effects of TLR4 are largely unknown and current data are controversial. Furthermore, very little is known regarding its function in cells other than myeloid cells and T cells. The objective of this study is to determine the function of SOCS3 in osteoblast inflammatory responses. We examined the effects of SOCS3 on E.coli LPS‐induced gene expression of matrix metalloproteinase 13 (MMP‐13), one of central regulators of bone resorption, by over‐expressing SOCS3 protein in osteoblasts via transient transfection and evaluated the effects by quantitative real‐time PCR, luciferase assay, and western blotting. We report for the first time that LPS stimulation of osteoblasts induces the transcriptional activation of MMP‐13. Importantly, we demonstrate that SOCS3 expression leads to a significant decrease of LPS‐induced MMP‐13 expression in both primary murine calvariae osteoblasts and a mouse osteoblast‐like cell line, MC3T3‐E1. Our findings implicate SOCS3 as an important regulatory mediator in bone inflammatory diseases by targeting MMP‐13.