title: Hydrogen sulfide attenuates IL-1β-induced inflammatory signaling and dysfunction of osteoarthritic chondrocytes.
abstract: Inflammatory cytokines are crucial factors in the onset of osteoarthritis (OA). The pro-inflammatory cytokine, interleukin-1β (IL-1β), is capable of stimulating a few cartilage degradation mediators and is of importance to the pathogenesis of OA. It has been demonstrated that hydrogen sulfide (H2S) exerts an inhibitory effect on inflammation. Thus, in the present study, we aimed to investigate the therapeutic effects of H2S in OA. For this purpose, an in vitro model of cartilage inflammation was created. Human OA chondrocytes were cultured and pre-treated with H2S (0.06-1.5 mM) with or without IL-1β (10 ng/ml) and then Griess reagent was used to quantify the production of nitric oxide (NO). Using enzyme-linked immunosorbent assay, we quantified the production of prostaglandin E2 (PGE2) and matrix metalloproteinase-13 (MMP-13). In addition, we determined the gene expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and MMP-13 using reverse transcription-quantitative polymerase chain reaction and the expression of signaling molecules related to mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) by western blot analysis. Our results revealed that H2S markedly reversed the effects of IL-1β on the gene expression of COX-2, MMP-13 and iNOS and on the production of MMP-13, PGE2 and NO. In addition, H2S inhibited the activation of the extracellular signal-regulated kinase (ERK)/IκBα/NF-κB pathway which was induced by IL-1β. On the whole, the results of the present study suggest that H2S exerts chondroprotective effects. Thus, H2S may have potential for use in the treatment of patients suffering from OA.
authors: Department of Joint Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266071, P.R. China.
authors: Chengzhi
authors: C
authors: Ha
authors: Department of Joint Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266071, P.R. China.
authors: Shaoqi
authors: S
authors: Tian
authors: Department of Joint Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266071, P.R. China.
authors: Kang
authors: K
authors: Sun
authors: Department of Joint Surgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
authors: Dawei
authors: D
authors: Wang
authors: Department of Joint Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266071, P.R. China.
authors: Jiangtao
authors: J
authors: Lv
authors: Department of Joint Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266071, P.R. China.
authors: Yuanhe
authors: Y
authors: Wang
mesh_terms: D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D015232:Dinoprostone; D006862:Hydrogen Sulfide