https://doi.org/10.4081/ejh.2022.3357
Inhibition of HMGB1 suppresses inflammation and catabolism in temporomandibular joint osteoarthritis via NF-κB signaling pathway
Submitted: 2 November 2021
Accepted: 24 May 2022
Published: 21 June 2022
Accepted: 24 May 2022
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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HMGB1 is a highly conserved nuclear protein that is rapidly released into the extracellular environment during infection or tissue damage. In osteoarthritis, HMGB1 acts as a pro-inflammatory cytokine inducing a positive feedback loop for synovial inflammation and cartilage degradation. The aim of this study was to explore the role of HMGB1 in inflammation and catabolism of temporomandibular joint osteoarthritis (TMJOA) and whether inhibition of HMGB1 affects TMJOA. Human synovial fibroblasts were incubated with HMGB1, the expression of pro-inflammatory cytokines and catabolic mediators were measured by Western blot and ELISA. NF-κB signaling pathway involvement was studied by the NF-κB inhibitor and detected by Western blotting and immunofluorescence staining. TMJOA was induced by an injection of Complete Freund’s adjuvant (CFA) into anterosuperior compartment of rat’s joint. An anti-HMGB1 antibody was used to assess the effect to HMGB1 in the synovium and cartilage of the CFA-induced TMJOA rats by H&E, Safranin O, Masson trichrome staining, immunohistochemistry and immunofluorescence. HMGB1 markedly increased the production of MMP13, ADAMTS5, IL-1β and IL-6 through activating NF-κB signaling pathway in human synovial fibroblasts. In vivo, application of the HMGB1 neutralizing antibody effectively ameliorated the detrimental extent of TMJOA. Furthermore, the HMGB1 neutralizing antibody reduced the expression of NF-κB, pro-inflammatory cytokines and catabolic mediators in the synovium and cartilage of CFA-induced TMJOA rats. HMGB1 inhibition alleviates TMJOA by reducing synovial inflammation and cartilage catabolism possibly through suppressing the NF-κB signaling pathway and may become a therapeutic method against TMJOA.
Wang XD, Zhang JN, Gan YH, Zhou YH. Current understanding of pathogenesis and treatment of TMJ osteoarthritis. J Dent Res 2015;94:666-73.
DOI: https://doi.org/10.1177/0022034515574770
Robinson W, Lepus C, Wang Q, Raghu H, Mao R, Lindstrom T, et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol 2016;12:580-92.
DOI: https://doi.org/10.1038/nrrheum.2016.136
Andersson U, Yang H, Harris H. High-mobility group box 1 protein (HMGB1) operates as an alarmin outside as well as inside cells. Sem Immunol 2018;38:40-8.
DOI: https://doi.org/10.1016/j.smim.2018.02.011
Nefla M, Holzinger D, Berenbaum F, Jacques C. The danger from within: alarmins in arthritis. Nat Rev Rheumatol 2016;12:669-83.
DOI: https://doi.org/10.1038/nrrheum.2016.162
Terada C, Yoshida A, Nasu Y, Mori S, Tomono Y, Tanaka M, et al. Gene expression and localization of high-mobility group box chromosomal protein-1 (HMGB-1) in human osteoarthritic cartilage. Acta Med Okayama 2011;65:369-77.
Ding L, Buckwalter J, Martin J. DAMPs Synergize with cytokines or fibronectin fragment on inducing chondrolysis but lose effect when acting alone. Mediators Inflamm 2017;2017:2642549.
DOI: https://doi.org/10.1155/2017/2642549
Li X, Li Y, Yang X, Liao R, Chen L, Guo Q, et al. PR11-364P22.2/ATF3 protein interaction mediates IL-1-induced catabolic effects in cartilage tissue and chondrocytes. J Cell Mol Med 2021;25:6188-202.
DOI: https://doi.org/10.1111/jcmm.16561
Liu-Bryan R, Terkeltaub R. Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol 2015;11:35-44.
DOI: https://doi.org/10.1038/nrrheum.2014.162
Goldring M, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol 2011;23:471-8.
DOI: https://doi.org/10.1097/BOR.0b013e328349c2b1
Loreto C, Filetti V, Almeida L, La Rosa G, Leonardi R, Grippaudo C, et al. MMP-7 and MMP-9 are overexpressed in the synovial tissue from severe temporomandibular joint dysfunction. Eur J Histochem 2020;64:3113.
DOI: https://doi.org/10.4081/ejh.2020.3113
Alquraini A, Jamal M, Zhang L, Schmidt T, Jay G, Elsaid K. The autocrine role of proteoglycan-4 (PRG4) in modulating osteoarthritic synoviocyte proliferation and expression of matrix degrading enzymes. Arthritis Res Ther 2017;19:89.
DOI: https://doi.org/10.1186/s13075-017-1301-5
de Seny D, Cobraiville G, Charlier E, Neuville S, Esser N, Malaise D, et al. Acute-phase serum amyloid a in osteoarthritis: regulatory mechanism and proinflammatory properties. PloS One 2013;8:e66769.
DOI: https://doi.org/10.1371/journal.pone.0066769
Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier J, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011;7:33-42.
DOI: https://doi.org/10.1038/nrrheum.2010.196
Musumeci D, Roviello GN, Montesarchio D. An overview on HMGB1 inhibitors as potential therapeutic agents in HMGB1-related pathologies. Pharmacol Ther 2014;141:347-57.
DOI: https://doi.org/10.1016/j.pharmthera.2013.11.001
Paudel YN, Angelopoulou E, Semple B, Piperi C, Othman I, Shaikh MF. Potential neuroprotective effect of the HMGB1 inhibitor glycyrrhizin in neurological disorders. ACS Chem Neurosci 2020;11:485-500.
DOI: https://doi.org/10.1021/acschemneuro.9b00640
Yang H, Wang H, Andersson U. Targeting inflammation driven by HMGB1. Front Immunol 2020;11:484.
DOI: https://doi.org/10.3389/fimmu.2020.00484
Pisetsky DS, Erlandsson-Harris H, Andersson U. High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheumatic disease. Arthritis Res Ther 2008;10:209.
DOI: https://doi.org/10.1186/ar2440
Feng Y, Fang W, Li C, Guo H, Li Y, Long X. The expression of high-mobility group box protein-1 in temporomandibular joint osteoarthritis with disc perforation. J Oral Pathol Med 2016;45:148-52.
DOI: https://doi.org/10.1111/jop.12336
de Souza R, Lovato da Silva C, Nasser M, Fedorowicz Z, Al-Muharraqi M. Interventions for the management of temporomandibular joint osteoarthritis. Cochrane Database Syst Rev 2012(4):CD007261.
DOI: https://doi.org/10.1002/14651858.CD007261.pub2
Shrestha B, Dunn L. The Declaration of Helsinki on medical research involving human subjects: A review of seventh revision. J Nepal Health Res Counc 2020;17:548-52.
DOI: https://doi.org/10.33314/jnhrc.v17i4.1042
Nagai H, Miyamoto Y, Nakata A, Hatakeyama S, Iwanami Y, Fukuda M. Isolation and characterization of synovial cells from the human temporomandibular joint. J Oral Pathol Med 2006;35:104-10.
DOI: https://doi.org/10.1111/j.1600-0714.2006.00369.x
Feng Y, Hu S, Liu L, Ke J, Long X. HMGB1 contributes to osteoarthritis of temporomandibular joint by inducing synovial angiogenesis. J Oral Rehabil 2021;48:551-9.
DOI: https://doi.org/10.1111/joor.13129
Kameoka S, Matsumoto K, Kai Y, Yonehara Y, Arai Y, Honda K. Establishment of temporomandibular joint puncture technique in rats using in vivo micro-computed tomography (R_mCT®). Dentomaxillofac Radiol 2010;39:441-5.
DOI: https://doi.org/10.1259/dmfr/37174063
Xu L, Guo H, Li C, Xu J, Fang W, Long X. A time-dependent degeneration manner of condyle in rat CFA-induced inflamed TMJ. Am J Transl Res 2016;8:556-67.
Liu X, Cai HX, Cao PY, Feng Y, Jiang HH, Liu L, et al. TLR4 contributes to the damage of cartilage and subchondral bone in discectomy-induced TMJOA mice. J Cell Mol Med 2020;24:11489-99.
DOI: https://doi.org/10.1111/jcmm.15763
Bland J, Altman D. Multiple significance tests: the Bonferroni method. BMJ 1995;310:170.
DOI: https://doi.org/10.1136/bmj.310.6973.170
Rigoglou S, Papavassiliou A. The NF-κB signalling pathway in osteoarthritis. Int J Biochem Cell Biol 2013;45:2580-4.
DOI: https://doi.org/10.1016/j.biocel.2013.08.018
Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol 2014;10:44-56.
DOI: https://doi.org/10.1038/nrrheum.2013.160
Musumeci G, Castrogiovanni P, Mazzone V, Szychlinska M, Castorina S, Loreto C. Histochemistry as a unique approach for investigating normal and osteoarthritic cartilage. Eur J Histochemi 2014;58:2371.
DOI: https://doi.org/10.4081/ejh.2014.2371
Mathiessen A, Conaghan P. Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Res Ther 2017;19:18.
DOI: https://doi.org/10.1186/s13075-017-1229-9
Abramson S, Attur M. Developments in the scientific understanding of osteoarthritis. Arthritis Res Ther 2009;11:227.
DOI: https://doi.org/10.1186/ar2655
Castrogiovanni P, Di Rosa M, Ravalli S, Castorina A, Guglielmino C, Imbesi R, et al. Moderate physical activity as a prevention method for knee osteoarthritis and the role of synoviocytes as biological key. Int J Mol Sci 2019;20:511.
DOI: https://doi.org/10.3390/ijms20030511
Wang P, Liu C, Yang X, Zhou Y, Wei X, Ji Q, et al. Effects of low-level laser therapy on joint pain, synovitis, anabolic, and catabolic factors in a progressive osteoarthritis rabbit model. Lasers Med Sci 2014;29:1875-85.
DOI: https://doi.org/10.1007/s10103-014-1600-x
Sasaki T, Liu K, Agari T, Yasuhara T, Morimoto J, Okazaki M, et al. Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson's disease. ExpNeurol 2016:220-31.
DOI: https://doi.org/10.1016/j.expneurol.2015.11.003
Schierbeck H, Lundbäck P, Palmblad K, Klevenvall L, Erlandsson-Harris H, Andersson U, et al. Monoclonal anti-HMGB1 (high mobility group box chromosomal protein 1) antibody protection in two experimental arthritis models. Mol Med 2011;17:1039-44.
DOI: https://doi.org/10.2119/molmed.2010.00264
Aulin C, Lassacher T, Palmblad K, Erlandsson Harris H. Early stage blockade of the alarmin HMGB1 reduces cartilage destruction in experimental OA. Osteoarthritis Cartilage 2020;28:698-707.
DOI: https://doi.org/10.1016/j.joca.2020.01.003
Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage 2013;21:16-21.
DOI: https://doi.org/10.1016/j.joca.2012.11.012
Maeda R, Kawasaki Y, Kume Y, Go H, Suyama K, Hosoya M. Involvement of high mobility group box 1 in the pathogenesis of severe hemolytic uremic syndrome in a murine model. Am J Physiol Renal Physiol 2019;317:F1420-9.
DOI: https://doi.org/10.1152/ajprenal.00263.2019
Haruma J, Teshigawara K, Hishikawa T, Wang D, Liu K, Wake H, et al. Anti-high mobility group box-1 (HMGB1) antibody attenuates delayed cerebral vasospasm and brain injury after subarachnoid hemorrhage in rats. Sci Rep 2016;6:37755.
DOI: https://doi.org/10.1038/srep37755
Andersson U, Erlandsson-Harris H. HMGB1 is a potent trigger of arthritis. J Intern Med 2004;255:344-50.
DOI: https://doi.org/10.1111/j.1365-2796.2003.01303.x
Lepetsos P, Papavassiliou K, Papavassiliou A. Redox and NF-κB signaling in osteoarthritis. Free Radic Biol Med 2019;132:90-100.
DOI: https://doi.org/10.1016/j.freeradbiomed.2018.09.025
Kobayashi H, Chang S, Mori D, Itoh S, Hirata M, Hosaka Y, et al. Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes. Nat Commun 2016;7:13336.
DOI: https://doi.org/10.1038/ncomms13336
Marcu K, Otero M, Olivotto E, Borzi R, Goldring M. NF-kappaB signaling: multiple angles to target OA. Curr Drug Targets 2010;11:599-613.
DOI: https://doi.org/10.2174/138945010791011938
Fu Y, Lei J, Zhuang Y, Zhang K, Lu D. Overexpression of HMGB1 A-box reduced IL-1β-induced MMP expression and the production of inflammatory mediators in human chondrocytes. Exp Cell Res 2016;349:184-90.
DOI: https://doi.org/10.1016/j.yexcr.2016.10.014
Lin SS, Yuan LJ, Niu CC, Tu YK, Yang CY, Ueng SWN. Hyperbaric oxygen inhibits the HMGB1/RAGE signaling pathway by upregulating Mir-107 expression in human osteoarthritic chondrocytes. Osteoarthritis Cartilage 2019;27:1372-81.
DOI: https://doi.org/10.1016/j.joca.2019.05.011
Ethics Approval
All experiments and sample collections were performed according to the standards of the Human Research Ethics Committee, School and Hospital of Stomatology, Wuhan University, Wuhan, China (protocol no. 2014LUNSHENZI24)Rights
National Natural Science Foundation of China, grant no. 81771100 to X. LongHow to Cite
Li, Y. Y., Feng, Y. P., Liu, L., Ke, J., & Long, X. (2022). Inhibition of HMGB1 suppresses inflammation and catabolism in temporomandibular joint osteoarthritis <em>via</em> NF-κB signaling pathway. European Journal of Histochemistry, 66(3). https://doi.org/10.4081/ejh.2022.3357
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