Hydrogen sulfide attenuates IL-1β-induced inflammatory signaling and dysfunction of osteoarthritic chondrocytes

Ha,Chengzhi; Tian,Shaoqi; Sun,Kang; Wang,Dawei; Lv,Jiangtao; Wang,Yuanhe

doi:10.3892/ijmm.2015.2183

Hydrogen sulfide attenuates IL-1β-induced inflammatory signaling and dysfunction of osteoarthritic chondrocytes

Authors:
- Chengzhi Ha
- Shaoqi Tian
- Kang Sun
- Dawei Wang
- Jiangtao Lv
- Yuanhe Wang
View Affiliations

Affiliations: Department of Joint Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266071, P.R. China, Department of Joint Surgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
Published online on: April 14, 2015 https://doi.org/10.3892/ijmm.2015.2183
Pages: 1657-1666

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Arden NK and Leyland KM: Osteoarthritis year 2013 in review: clinical. Osteoarthritis Cartilage. 21:1409–1413. 2013. View Article : Google Scholar : PubMed/NCBI
2	Sulzbacher I: Osteoarthritis: histology and pathogenesis. Wien Med Wochenschr. 163:212–219. 2013. View Article : Google Scholar
3	Berenbaum F: Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 21:16–21. 2013. View Article : Google Scholar
4	Wojdasiewicz P, Poniatowski LA and Szukiewicz D: The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm. 2014:5614592014. View Article : Google Scholar : PubMed/NCBI
5	Balaganur V, Pathak NN, Lingaraju MC, et al: Chondroprotective and anti-inflammatory effects of S-methylisothiourea, an inducible nitric oxide synthase inhibitor in cartilage and synovial explants model of osteoarthritis. J Pharm Pharmacol. 66:1021–1031. 2014. View Article : Google Scholar : PubMed/NCBI
6	Goldring MB, Otero M, Plumb DA, et al: Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur Cell Mater. 21:202–220. 2011.PubMed/NCBI
7	Verhagen AP, Bierma-Zeinstra SM, Boers M, et al: Balneotherapy for osteoarthritis. Cochrane Database Syst Rev. 4:CD0068642007.PubMed/NCBI
8	Ekundi-Valentim E, Santos KT, Camargo EA, Denadai-Souza A, Teixeira SA, Zanoni CI, Grant AD, Wallace J, Muscará MN and Costa SK: Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat. Br J Pharmacol. 159:1463–1474. 2010. View Article : Google Scholar : PubMed/NCBI
9	Costantino M, Filippelli A, Quenau P, Nicolas JP and Coiro V: Sulphur mineral water and SPA therapy in osteoarthritis. Therapie. 67:43–48. 2012.In French. View Article : Google Scholar : PubMed/NCBI
10	Kloesch B, Liszt M and Broell J: H₂S transiently blocks IL-6 expression in rheumatoid arthritic fibroblast-like synoviocytes and deactivates p44/42 mitogen-activated protein kinase. Cell Biol Int. 34:477–484. 2010. View Article : Google Scholar : PubMed/NCBI
11	Wang R: Hydrogen sulfide: the third gasotransmitter in biology and medicine. Antioxid Redox Signal. 12:1061–1064. 2010. View Article : Google Scholar
12	Lowicka E and Beltowski J: Hydrogen sulfide (H₂S) - the third gas of interest for pharmacologists. Pharmacol Rep. 59:4–24. 2007.
13	Li L, Fox B, Keeble J, et al: The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells. J Cell Mol Med. 17:365–376. 2013. View Article : Google Scholar : PubMed/NCBI
14	Fox B, Schantz JT, Haigh R, et al: Inducible hydrogen sulfide synthesis in chondrocytes and mesenchymal progenitor cells: is H S a novel cytoprotective mediator in the inflamed joint? J Cell Mol Med. 16:896–910. 2012. View Article : Google Scholar
15	Whiteman M, Haigh R, Tarr JM, Gooding KM, Shore AC and Winyard PG: Detection of hydrogen sulfide in plasma and knee-joint synovial fluid from rheumatoid arthritis patients: relation to clinical and laboratory measures of inflammation. Ann NY Acad Sci. 1203:146–150. 2010. View Article : Google Scholar : PubMed/NCBI
16	Andruski B, McCafferty DM, Ignacy T, Millen B and McDougall JJ: Leukocyte trafficking and pain behavioral responses to a hydrogen sulfide donor in acute monoarthritis. Am J Physiol Regul Integr Comp Physiol. 295:R814–R820. 2008. View Article : Google Scholar : PubMed/NCBI
17	Rigoglou S and Papavassiliou AG: The NF-κB signalling pathway in osteoarthritis. Int J Biochem Cell Biol. 45:2580–2584. 2013. View Article : Google Scholar : PubMed/NCBI
18	Kloesch B, Liszt M, Krehan D, Broell J, Kiener H and Steiner G: High concentrations of hydrogen sulphide elevate the expression of a series of pro-inflammatory genes in fibroblast-like synoviocytes derived from rheumatoid and osteoarthritis patients. Immunol Lett. 141:197–203. 2012. View Article : Google Scholar
19	Jiang B, Xu S, Hou X, Pimentel DR, Brecher P and Cohen RA: Temporal control of NF-kappaB activation by ERK differentially regulates interleukin-1beta-induced gene expression. J Biol Chem. 279:1323–1329. 2004. View Article : Google Scholar
20	Zhi L, Ang AD, Zhang H, Moore PK and Bhatia M: Hydrogen sulfide induces the synthesis of proinflammatory cytokines in human monocyte cell line U937 via the ERK-NF-kappaB pathway. J Leukoc Biol. 81:1322–1332. 2007. View Article : Google Scholar : PubMed/NCBI
21	Stolz M, Gottardi R, Raiteri R, et al: Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy. Nat Nanotechnol. 4:186–192. 2009. View Article : Google Scholar : PubMed/NCBI
22	Gossan N, Zeef L, Hensman J, et al: The circadian clock in murine chondrocytes regulates genes controlling key aspects of cartilage homeostasis. Arthritis Rheum. 65:2334–2345. 2013. View Article : Google Scholar : PubMed/NCBI
23	Tsubota M and Kawabata A: Role of hydrogen sulfide, a gasotransmitter, in colonic pain and inflammation. Yakugaku Zasshi. 134:1245–1252. 2014.In Japanese. View Article : Google Scholar
24	Houard X, Goldring MB and Berenbaum F: Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis. Curr Rheumatol Rep. 15:3752013. View Article : Google Scholar : PubMed/NCBI
25	Wang X, Li F, Fan C, Wang C and Ruan H: Effects and relationship of ERK1 and ERK2 in interleukin-1β-induced alterations in MMP3, MMP13, type II collagen and aggrecan expression in human chondrocytes. Int J Mol Med. 27:583–589. 2011.PubMed/NCBI
26	Szabo C: Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov. 6:917–935. 2007. View Article : Google Scholar : PubMed/NCBI
27	Kimura H: The physiological role of hydrogen sulfide and beyond. Nitric Oxide. 41:4–10. 2014. View Article : Google Scholar : PubMed/NCBI
28	Ang SF, Moochhala SM, MacAry PA and Bhatia M: Hydrogen sulfide and neurogenic inflammation in polymicrobial sepsis: involvement of substance P and ERK-NF-κB signaling. PLoS One. 6:e245352011. View Article : Google Scholar
29	Bentz M, Zaouter C, Shi Q, et al: Inhibition of inducible nitric oxide synthase prevents lipid peroxidation in osteoarthritic chondrocytes. J Cell Biochem. 113:2256–2267. 2012. View Article : Google Scholar : PubMed/NCBI
30	Hu LF, Wong PT, Moore PK and Bian JS: Hydrogen sulfide attenuates lipopolysaccharide-induced inflammation by inhibition of p38 mitogen-activated protein kinase in microglia. J Neurochem. 100:1121–1128. 2007. View Article : Google Scholar : PubMed/NCBI
31	Jeong SO, Pae HO, Oh GS, et al: Hydrogen sulfide potentiates interleukin-1beta-induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells. Biochem Biophys Res Commun. 345:938–944. 2006. View Article : Google Scholar : PubMed/NCBI
32	Zhang RX, Ren K and Dubner R: Osteoarthritis pain mechanisms: basic studies in animal models. Osteoarthritis Cartilage. 21:1308–1315. 2013. View Article : Google Scholar : PubMed/NCBI
33	de Boer TN, Huisman AM, Polak AA, et al: The chondroprotective effect of selective COX-2 inhibition in osteoarthritis: ex vivo evaluation of human cartilage tissue after in vivo treatment. Osteoarthritis Cartilage. 17:482–488. 2009. View Article : Google Scholar
34	Li X, Ellman M, Muddasani P, et al: Prostaglandin E2 and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis. Arthritis Rheum. 60:513–523. 2009. View Article : Google Scholar : PubMed/NCBI
35	Distrutti E, Sediari L, Mencarelli A, et al: Evidence that hydrogen sulfide exerts antinociceptive effects in the gastrointestinal tract by activating KATP channels. J Pharmacol Exp Ther. 316:325–335. 2006. View Article : Google Scholar
36	Kawabata A, Ishiki T, Nagasawa K, et al: Hydrogen sulfide as a novel nociceptive messenger. Pain. 132:74–81. 2007. View Article : Google Scholar : PubMed/NCBI
37	Rosa SC, Rufino AT, Judas FM, Tenreiro CM, Lopes MC and Mendes AF: Role of glucose as a modulator of anabolic and catabolic gene expression in normal and osteoarthritic human chondrocytes. J Cell Biochem. 112:2813–2824. 2011. View Article : Google Scholar : PubMed/NCBI
38	Vacek TP, Qipshidze N and Tyagi SC: Hydrogen sulfide and sodium nitroprusside compete to activate/deactivate MMPs in bone tissue homogenates. Vasc Health Risk Manag. 9:117–123. 2013.PubMed/NCBI
39	Shakibaei M, Csaki C, Nebrich S and Mobasheri A: Resveratrol suppresses interleukin-1beta-induced inflammatory signaling and apoptosis in human articular chondrocytes: potential for use as a novel nutraceutical for the treatment of osteoarthritis. Biochem Pharmacol. 76:1426–1439. 2008. View Article : Google Scholar : PubMed/NCBI
40	Ding QH, Cheng Y, Chen WP, Zhong HM and Wang XH: Celastrol, an inhibitor of heat shock protein 90β potently suppresses the expression of matrix metalloproteinases, inducible nitric oxide synthase and cyclooxygenase-2 in primary human osteoarthritic chondrocytes. Eur J Pharmacol. 708:1–7. 2013. View Article : Google Scholar : PubMed/NCBI
41	Perry MM, Hui CK, Whiteman M, et al: Hydrogen sulfide inhibits proliferation and release of IL-8 from human airway smooth muscle cells. Am J Respir Cell Mol Biol. 45:746–752. 2011. View Article : Google Scholar : PubMed/NCBI
42	Kloesch B, Liszt M, Steiner G and Broll J: Inhibitors of p38 and ERK1/2 MAPkinase and hydrogen sulphide block constitutive and IL-1β-induced IL-6 and IL-8 expression in the human chondrocyte cell line C-28/I2. Rheumatol Int. 32:729–736. 2012. View Article : Google Scholar
43	Zhang H, Moochhala SM and Bhatia M: Endogenous hydrogen sulfide regulates inflammatory response by activating the ERK pathway in polymicrobial sepsis. J Immunol. 181:4320–4331. 2008. View Article : Google Scholar : PubMed/NCBI
44	Sieghart D, Kiener HP, Kloesch B and Steiner G: A9.3 Hydrogen sulfide and MEK1 inhibition reduce IL-1beta-induced activation of fibroblast-like synoviocytes. Ann Rheum Dis. 73:A932014. View Article : Google Scholar
45	Oh GS, Pae HO, Lee BS, et al: Hydrogen sulfide inhibits nitric oxide production and nuclear factor-kappaB via heme oxygenase-1 expression in RAW264.7 macrophages stimulated with lipopolysaccharide. Free Radic Biol Med. 41:106–119. 2006. View Article : Google Scholar : PubMed/NCBI