title: Overexpression of HMGB1 A-box reduced IL-1β-induced MMP expression and the production of inflammatory mediators in human chondrocytes.
abstract: The pro-inflammatory cytokine interleukin-1 beta (IL-1β) plays a crucial role in the pathogenesis of osteoarthritis (OA) by stimulating several mediators that contribute to cartilage degradation. The aim of this study was to investigate the effects and mechanism of high mobility group box 1 (HMGB1) inhibitors HMGB1 A-box on the expression of matrix metalloproteinase (MMP) and the production of inflammatory mediators in human osteoarthritis chondrocytes after activation by IL-1β. We found that the overexpression of HMGB1 A-box significantly decreased the IL-1β-stimulated the production of MMP-1, MMP-3 and MMP-9, and also reduced the elevated levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) associated with the inhibition of prostaglandin E2 (PGE2) and nitric oxide (NO) production in IL-1β-stimulated chondrocytes. In addition, overexpression of the HMGB1 A-box significantly inhibited the up-regulation of ADAMTS-4, ADAMTS-5 and HMGB1 caused by IL-1β in chondrocytes. Moreover, the overexpression of HMGB1 A-box markedly suppressed the IL-1β-mediated activation of the Toll-like receptor 4 (TRL4)/NF-κB pathway. Our observations indicated that the HMGB1 A-box can play a protective role by suppressing the IL-1β-induced expression of MMPs and that the production of inflammatory mediators in chondrocytes was associated with suppression of the HMGB1/TLR4/NF-κB pathway. In conclusion, HMGB1 A-box relieves the development of OA that may be associated with regulating the HMGB1/TLR4/NF-κB pathway.
authors: Department of Orthopaedic Trauma, Xi'an Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710054, PR China.
authors: Yahui
authors: Y
authors: Fu
authors: Department of Orthopaedic Trauma, Xi'an Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710054, PR China. Electronic address: leijinlai@126.com.
authors: Jinlai
authors: J
authors: Lei
authors: Department of Orthopaedic Trauma, Xi'an Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710054, PR China.
authors: Yan
authors: Y
authors: Zhuang
authors: Department of Orthopaedic Trauma, Xi'an Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710054, PR China.
authors: Kun
authors: K
authors: Zhang
authors: Department of Orthopaedic Trauma, Xi'an Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710054, PR China.
authors: Daigang
authors: D
authors: Lu
mesh_terms: D000071096:ADAMTS Proteins / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D000071096:ADAMTS Proteins; D020782:Matrix Metalloproteinases; D015232:Dinoprostone
keywords: High mobility group box 1 A-box (HMGB1 A-box); Matrix metalloproteinase (MMP); Nuclear factor-kappa B (NF-κB); Osteoarthritis (OA); Toll-like receptor 4 (TRL4)