title: A critical role for suppressors of cytokine signaling 3 in regulating LPS-induced transcriptional activation of matrix metalloproteinase-13 in osteoblasts.
abstract: Suppressor 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 actions of IL-6 family of cytokines and anti-inflammatory signaling of IL-10 by negatively regulating gp130/Jak/Stat3 signal transduction, how and the molecular mechanisms whereby SOCS3 controls the downstream impact of TLR4 are largely unknown and current data are controversial. Furthermore, very little is known regarding SOCS3 function in cells other than myeloid cells and T cells. Our previous study demonstrates that SOCS3 is expressed in osteoblasts and functions as a critical inhibitor of LPS-induced IL-6 expression. However, the function of SOCS3 in osteoblasts remains largely unknown. In the current study, we report for the first time that LPS stimulation of osteoblasts induces the transcriptional activation of matrix metalloproteinase (MMP)-13, a central regulator of bone resorption. Importantly, we demonstrate that SOCS3 overexpression 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.
authors: Department of Periodontology, The Forsyth Institute , Cambridge , MA , United States.
authors: Anqi
authors: A
authors: Gao
authors: Alpdogan
authors: A
authors: Kantarci
authors: Bruno Schneider
authors: BS
authors: Herrera
authors: Hongwei
authors: H
authors: Gao
authors: Thomas E
authors: TE
authors: Van Dyke
keywords: Cytokine; Inflammation; Osteoblasts; Periodontitis
references: Infect Immun. 1999 Jun;67(6):2841-6
references: 10338489
references: Nat Immunol. 2003 Jun;4(6):546-50
references: 12754506
references: Am J Physiol. 1993 Mar;264(3 Pt 1):E391-7
references: 8460686
references: J Immunol. 2001 Mar 1;166(5):3574-9
references: 11207318
references: J Bone Miner Res. 2004 Nov;19(11):1905-16
references: 15476591
references: J Immunol. 2005 Mar 1;174(5):3024-31
references: 15728516
references: Nat Immunol. 2003 Jun;4(6):551-6
references: 12754507
references: J Dent Res. 2006 Jul;85(7):584-95
references: 16798857
references: Arthritis Rheum. 2008 Dec;58(12):3742-52
references: 19035473
references: Nat Med. 2003 Aug;9(8):1047-54
references: 12847520
references: Development. 2004 Dec;131(23):5883-95
references: 15539485
references: Immunol Cell Biol. 2012 Jan;90(1):124-9
references: 21519345
references: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17192-7
references: 15563592
references: J Endocrinol. 2009 Jun;201(3):309-20
references: 19443863
references: Biochimie. 2013 Apr;95(4):922-33
references: 23277113
references: J Biol Chem. 2010 Nov 26;285(48):37227-39
references: 20876575
references: J Immunol. 2002 Aug 1;169(3):1516-23
references: 12133979
references: J Clin Invest. 2006 Jun;116(6):1571-81
references: 16710471
references: J Immunol. 2002 Sep 15;169(6):3353-62
references: 12218157
references: J Biol Chem. 1999 Apr 16;274(16):10689-92
references: 10196138
references: FASEB J. 1991 May;5(8):2145-54
references: 1850705
references: Int Endod J. 2013 Jul;46(7):666-74
references: 23331101
references: Mol Immunol. 2008 Mar;45(5):1405-13
references: 17920684
references: J Biol Chem. 1990 Dec 25;265(36):22342-7
references: 2176215
references: J Periodontol. 2013 Nov;84(11):1683-9
references: 23368947
references: J Immunol. 2006 Aug 1;177(3):1879-85
references: 16849500
references: Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9324-9
references: 11481489
references: Nat Immunol. 2003 Jun;4(6):540-5
references: 12754505
references: FASEB J. 1998 Sep;12(12):1075-95
references: 9737711
references: Arthritis Rheum. 2012 Oct;64(10):3313-23
references: 22576756
references: Vaccine. 2003 Jun 1;21 Suppl 2:S61-7
references: 12763685
references: Growth Factors. 2012 Aug;30(4):207-19
references: 22574771
references: Blood. 1999 Oct 15;94(8):2880-9
references: 10515892
references: J Endotoxin Res. 2007;13(2):85-93
references: 17621549
references: Infect Immun. 1996 Jul;64(7):2371-80
references: 8698454
references: Laryngoscope. 2007 May;117(5):841-7
references: 17473680
references: J Dent Res. 2011 Feb;90(2):157-62
references: 21270460
references: Mod Rheumatol. 2004;14(3):197-204
references: 17143675
references: Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5004-9
references: 22411837
references: J Clin Invest. 2001 Dec;108(12):1781-8
references: 11748261
references: J Biol Chem. 2002 Mar 8;277(10):7865-74
references: 11751895
references: Keio J Med. 2009 Jun;58(2):73-83
references: 19597303
references: J Clin Invest. 2007 Jan;117(1):122-32
references: 17173138