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Role of proinflammatory cytokines in the pathophysiology of osteoarthritis
Abstract
Osteoarthritis (OA) is associated with cartilage destruction, subchondral bone remodeling and inflammation of the synovial membrane, although the etiology and pathogenesis underlying this debilitating disease are poorly understood. Secreted inflammatory molecules, such as proinflammatory cytokines, are among the critical mediators of the disturbed processes implicated in OA pathophysiology. Interleukin (IL)-1β and tumor necrosis factor (TNF), in particular, control the degeneration of articular cartilage matrix, which makes them prime targets for therapeutic strategies. Animal studies provide support for this approach, although only a few clinical studies have investigated the efficacy of blocking these proinflammatory cytokines in the treatment of OA. Apart from IL-1β and TNF, several other cytokines including IL-6, IL-15, IL-17, IL-18, IL-21, leukemia inhibitory factor and IL-8 (a chemokine) have also been shown to be implicated in OA and could possibly be targeted therapeutically. This Review discusses the current knowledge regarding the role of proinflammatory cytokines in the pathophysiology of OA and addresses the potential of anticytokine therapy in the treatment of this disease.
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“Because TNF-α signaling primarily via TNFR1 binds TRADD and RIPK1 to generate complexes that activate NF-κB, MAPKs, and caspases, IL-1β and TNF-α cooperate to enhance chronic inflammation in degenerative joint disease [42,43].”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [42]
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Jin, J., Liu, Y., Jiang, C., Shen, Y., Chu, G., Liu, C., Jiang, L., Huang, G., Qin, Y., Zhang, Y., et al. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100370 · Cited by 38
Tang, S., Cao, Y., Cai, Z.-P., Nie, X., Ruan, J., Zhou, Z., Ruan, G., Zhu, Z.-H., Han, W., & Ding, C. (2022) · Science Signaling · doi:10.1126/scisignal.abm6265 · Cited by 40
“Some of them, such as lncRNA-cartilage injury- related (CIR) and p50-associated cyclooxygenase 2-extragenic RNA (PACER), contribute to ECM degradation and OA progression (17, 18).”
BackgroundResultInfluentialAutophagy deficiency exacerbates acute lung injury induced by copper oxide nanoparticles
Xiao, J., Tu, B.-J., Zhou, X., Jiang, X.-J., Xu, G., Zhang, J., Qin, X., Sumayyah, G., Fan, J., Wang, B., et al. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-00909-1 · Cited by 40
“In particular, IL-1β, TNF-α, and IL-6 are recognized as the major proinflammatory cytokines [19].”
BackgroundJuglanin inhibits IL-1β-induced inflammation in human chondrocytes
Chen, X.-X., Zhang, C., Wang, X., & Huo, S.-S. (2019) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2019.1657877 · Cited by 40
“IL-1b stimulation promotes gene expression and protein secretion of other pro-inflammatory factors and chemokines such as IL-6 and TNF-a, which may induce secondary insults to chondrocytes [16].”
BackgroundThe hsa-miR-181a-5p reduces oxidation resistance by controlling SECISBP2 in osteoarthritis
Xue, J., Min, Z., Xia, Z., Cheng, B., Lan, B.-S., Zhang, F., Han, Y., Wang, K.-Z., & Sun, J. (2018) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-018-2273-6 · Cited by 40
Sodium butyrate abolishes the degradation of type II collagen in human chondrocytes
Wang, B., Zhou, J., & Wang, K. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.03.062 · Cited by 43
Stancker, T. G., Vieira, S. S., Serra, A., Lima, R. D. N., Feliciano, R. D. S., Silva, J., dos Santos, S. A., Vieira, M. A. D. S., Simões, M. C. B., Leal-Junior, E. C., et al. (2018) · Lasers in Medical Science · doi:10.1007/s10103-018-2466-0 · Cited by 40
FABP4 as a biomarker for knee osteoarthritis.
Zhang, C.-F., Li, T., Chiu, K., Wen, C., Xu, A., & Yan, C.-H. (2018) · Biomarkers in Medicine · doi:10.2217/bmm-2017-0207 · Cited by 40
Ma, C.-H., Lv, Q., Yu, Y.-X., Zhang, Y., Kong, D., Niu, K., & Yi, C. (2015) · Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · doi:10.1590/1414-431x20154407 · Cited by 40
“Studies have revealed that the pathophysiology of OA involves proinflammatory cytokines, such as interleukin1b, tumor necrosis factor (TNF)-a, and interleukin-6 (9).”
BackgroundCao, Y.-X., Zhang, X., Shang, W., Xu, J.-J., Wang, X.-H., Hu, X.-Q., Ao, Y., & Cheng, H.-P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066444 · Cited by 40
“IL-1b or TNF-a Simulated Superoxide Flash Activity in Cultured Chondrocytes IL-1b and TNF-a are two main proinflammatory cytokines linked to cartilage destruction [25,26].”
Venkatesan, N., Barré, L., Bourhim, M., Magdalou, J., Mainard, D., Netter, P., Fournel‐Gigleux, S., & Ouzzine, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034020 · Cited by 40
The potential role of GLP ‐1 receptor agonists in osteoarthritis
Ryan, M., Megyeri, S., Nuffer, W. A., & Trujillo, J. M. (2025) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.70005 · Cited by 44
“13,15”
Caliogna, L., Berni, M., Torriani, C., Mancuso, M. E., Di Minno, M. N. D., Brancato, A. M., Jannelli, E., Mosconi, M., & Pasta, G. (2024) · Haemophilia · doi:10.1111/hae.15097 · Cited by 39
Natural Compounds Affecting Inflammatory Pathways of Osteoarthritis
Lee, Y.-T., Yunus, M. H. M., Ugusman, A., & Yazid, M. (2022) · Antioxidants · doi:10.3390/antiox11091722 · Cited by 39
“This factor is initiated by various inflammatory cytokines such as IL-1β, TNF-α, and IL-6; severe mechanical stressors; or the breakdown products of ECM that can promote the transcription of the catabolic gene and also stimulate the production of inflammatory mediators through a positive feedback loop [29,30].”
BackgroundDu, K.-W., Fang, X.-C., & Li, Z. (2021) · Immunity, Inflammation and Disease · doi:10.1002/iid3.424 · Cited by 39
“Additionally, chondrocytes also secret pro‐inflammatory cytokines including IL‐6 and other inflammatory regulators during osteoarthritis progression resulting in disrupted homeostasis of the cartilage.(16) In this study, we took advantage of IL‐1β‐induced osteoarthritis chondrocyte degeneration to model osteoarthritis…”
BackgroundNummenmaa, E., Hämäläinen, M., Pemmari, A., Moilanen, L. J., Tuure, L., Nieminen, R., Moilanen, T., Vuolteenaho, K., & Moilanen, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010087 · Cited by 39
He, Z.-N., Nie, P., Lu, J., Ling, Y.-J., Guo, J., Zhang, B., Hu, J., Liao, J., Gu, J., Dai, B., et al. (2020) · Bone & Joint Research · doi:10.1302/2046-3758.910.bjr-2019-0368.r2 · Cited by 39
Bai, H., Zhang, Z.-H., Li, Y., Song, X.-P., Ma, T.-W., Liu, C.-P., Liu, L., Yuan, R., Wang, X., & Gao, L. (2020) · Nutrients · doi:10.3390/nu12071988 · Cited by 39
“IL-1β is a pro-inflammatory factor found in synovial fluid and cartilage during OA development, and induces the production of catabolic mediators [4], such as matrix metalloproteinases (MMPs), which degrade proteoglycans and type II collagen, and is a component of extracellular matrix (ECM) scaffolds [5].”
BackgroundReed, K., Ulici, V., Kim, C., Chubinskaya, S., Loeser, R., & Phanstiel, D. (2020) · bioRxiv · doi:10.1101/2020.06.18.155390 · Cited by 39
Park, M., Jung, J.-C., Hill, S., Cartwright, E., Dohnalek, M., Yu, M., Jun, H. J., Han, S., Hong, J., & Son, D.-J. (2020) · Nutrients · doi:10.3390/nu12040956 · Cited by 39
“Increasing evidence has demonstrated that the significantly elevated levels of pro-inflammatory cytokines observed in OA patients play a critical role in the promotion of the catabolic processes in OA, causing cartilage degradation [62,63].”
BackgroundJian, Y., Ding, W., Wu, N., Jiang, S., & Li, W. (2019) · BioMed Research International · doi:10.1155/2019/2629791 · Cited by 44
“Many studies demonstrated that patients with OA have an elevated level of IL-1β than normal people [13], and blocking IL-1β production could counteract the degradative mechanisms associated with OA pathology [26].”
BackgroundThe CNS theory of osteoarthritis: Opportunities beyond the joint
Morris, J. L., Letson, H. L., Gillman, R., Hazratwala, K., Wilkinson, M., McEwen, P. J. C., & Dobson, G. P. (2019) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2019.03.008 · Cited by 50
Sharma, N., Drobinski, P., Kayed, A., Chen, Z.-Z., Kjelgaard-Petersen, C., Gantzel, T., Karsdal, M., Michaelis, M., Ladel, C., Bay-Jensen, A., et al. (2019) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2019.11.002 · Cited by 39
Pattappa, G., Schewior, R., Hofmeister, I., Seja, J., Zellner, J., Johnstone, B., Docheva, D., & Angele, P. (2019) · Cells · doi:10.3390/cells8080936 · Cited by 39
Zheng, W., Feng, Z.-H., Lou, Y., Chen, C., Zhang, C., Tao, Z., Li, H., Cheng, L., & Ying, X. (2017) · OncoTarget · doi:10.18632/oncotarget.20587 · Cited by 39
“As shown in Figure 4A-4E, chondrocytes showed obvious up-regulation of the mRNA expression of MMP-1, MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 after IL-1β stimulation in contrast with the control group.”
BackgroundInfluentialAdipokines induce pro‐inflammatory factors in activated Cd4+ T cells from osteoarthritis patient
Scotece, M., Pérez, T., Conde, J., Abella, V., López, V., Pino, J., González-Gay, M., Gómez-Reino, J., Mera, A., Gómez, R., et al. (2017) · Journal of Orthopaedic Research · doi:10.1002/jor.23377 · Cited by 39
Taşoğlu, Ö., Şahin, A., Karataş, G., Koyuncu, E., Taşoğlu, I., Tecimel, O., & Özgirgin, N. (2017) · Medicine · doi:10.1097/md.0000000000006073 · Cited by 39
“It is also known that IL-1, IL-6, IL-15, and TNF-a can also be found in the serum of patients with OA.([8,9]) Several inflammatory mediators, especially IL-6 is known to stimulate platelet production frommegakaryocytes.”
BackgroundZhang, P., Zhong, Z.-H., Yu, H.-T., & Liu, B. (2015) · Scandinavian Journal of Rheumatology · doi:10.3109/03009742.2015.1009942 · Cited by 39
“Gene therapy has been suggested as a potential solution to overcome this limitation, with the expectation that eventually anti-arthritic proteins may be designed to be produced intra-articularly (26).”
BackgroundA Novel Rose Hip Preparation with Enhanced Anti-Inflammatory and Chondroprotective Effects
Schwager, J., Richard, N., Schoop, R., & Wolfram, S. (2014) · Mediators of Inflammation · doi:10.1155/2014/105710 · Cited by 39
“Theproinflammatory interleukin- (IL-) 1β has a key role in inducing the OA phenotype in chondrocytes [3].”
BackgroundKataoka, Y., Ariyoshi, W., Okinaga, T., Kaneuji, T., Mitsugi, S., Takahashi, T., & Nishihara, T. (2013) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2013.02.043 · Cited by 39
Lee, M., Won, Y., Shin, Y., Kim, J.-H., & Chun, J.-S. (2016) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2015.07.016 · Cited by 39
3 – Traumatic Arthritis and Posttraumatic Osteoarthritis in the Horse
McIlwraith, C. (2016) · doi:10.1016/b978-1-4557-5969-9.00003-6 · Cited by 39
Baek, A., Kim, Y., Lee, J. W., Lee, S. C., & Cho, S.-R. (2018) · Cell Transplantation · doi:10.1177/0963689718804130 · Cited by 39
Research progress on pharmacokinetics, anti-inflammatory and immunomodulatory effects of kaempferol.
Li, S.-R., Wang, S.-W., Zhang, L., Ka, Y., Zhou, M.-J., Wang, Y.-W., Tang, Z., Zhang, J., Wang, W., & Liu, W. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114387 · Cited by 38
Chen, Z., Pang, Q.-M., Zhan, J., Liu, J., Zhao, W., Dong, L., & Huang, W. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101340 · Cited by 26
Nims, R. J., Palmer, D. R., Kassab, J. G., Zhang, B., & Guilak, F. (2024) · The FASEB Journal · doi:10.1096/fj.202400883r · Cited by 46
Targeting NR1D1 in organ injury: challenges and prospects
Zhangsun, Z., Xu, X., Escames, G., Lei, W., Zhao, L., Zhou, Y., Tian, Y., Ren, Y., Acuña-Castroviejo, D., & Yang, Y. (2023) · Military Medical Research · doi:10.1186/s40779-023-00495-3 · Cited by 29
New treatment for osteoarthritis: Gene therapy
Li, X., Shen, L., Deng, Z., & Huang, Z. (2023) · Precision Clinical Medicine · doi:10.1093/pcmedi/pbad014 · Cited by 37
Epigenetics as a Therapeutic Target in Osteoarthritis
Núñez-Carro, C., Blanco-Blanco, M., Villagrán-Andrade, K. M., Blanco, F., & de Andrés, M. D. (2023) · Pharmaceuticals · doi:10.3390/ph16020156 · Cited by 38
Ye, P., Mi, Z.-H., Wei, D., Gao, P., Ma, M., & Yang, H.-B. (2022) · Stem Cells International · doi:10.1155/2022/9455152 · Cited by 38
“that activation of inflammatory factors, including IL1β, TNF-α, and IL-6 [48], is implicated in the development and progression of and OA [49, 50], while the blockage of these proinflammatory cytokines serves as an appealing treatment option for OA [51].”
BackgroundThe Role of Inflammasomes in Osteoarthritis and Secondary Joint Degeneration Diseases
Roškar, S., & Hafner‐Bratkovič, I. (2022) · Life · doi:10.3390/life12050731 · Cited by 47
“It has already been shown that the synovial fibroblasts, as the most abundant cells in the synovial membrane, release proinflammatory cytokines such as IL-1β and TNFα [97,98].”
BackgroundKhan, Z. U., Razzaq, A., Khan, A., Rehman, N. U., Khan, H., Khan, T., Khan, A. U., Althobaiti, N., Menaa, F., Iqbal, H., et al. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14020409 · Cited by 38
Kim, H., Seo, J., Lee, Y.-H., Park, K., Perry, T. A., Arden, N., Mobasheri, A., & Choi, H. (2022) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x221085952 · Cited by 38
Wang, Y., Li, T. X., Yang, Q., Feng, B., Xiang, Y., Lv, Z., & Weng, X. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108138 · Cited by 38
The emerging role of lncRNAs in chondrocytes from osteoarthritis patients.
Tu, J., Huang, W., Zhang, W.-W., Mei, J.-W., & Zhu, C. (2020) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2020.110642 · Cited by 38
Warner, S., Nair, A., Marpadga, R., Chubinskaya, S., Doherty, M., Valdes, A., & Scanzello, C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01385 · Cited by 38
“The inflammatory response has been shown to play an important role in osteoarthritis (OA) (1), both in symptomatic and structural manifestations, but the relative importance of specific inflammatory mediators in OA joints is yet to be fully elucidated.”
BackgroundTu, Y.-H., Ma, T., Wen, T., Yang, T., Xue, L., Cai, M.-W., Wang, F.-X., Guan, M.-Y., & Xue, H. (2019) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2019.11.186 · Cited by 38
Activation of the P38/CREB/MMP13 axis is associated with osteoarthritis
Ji, B., Ma, Y., Wang, H., Fang, X.-Q., & Shi, P.-H. (2019) · Drug Design, Development and Therapy · doi:10.2147/dddt.s209626 · Cited by 38
Pharmaceutical Effects of Inhibiting the Soluble Epoxide Hydrolase in Canine Osteoarthritis
McReynolds, C., Hwang, S., Yang, J., Wan, D.-B., Wagner, K., Morisseau, C., Li, D.-Y., Schmidt, W., & Hammock, B. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00533 · Cited by 38
Enhanced Antiarthritic Efficacy by Nanoparticles of (−)-Epigallocatechin Gallate–Glucosamine–Casein
Zheng, Y., Xiao, L., Yu, C.-H., Jin, P. K., Qin, D., Xu, Y., Yin, J., Liu, Z., & Du, Q. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b02075 · Cited by 40
Yin, S.-J., Zhang, L., Ding, L., Huang, Z.-Q., Xu, B., Li, X.-C., Wang, P.-M., & Mao, J. (2018) · Journal of Inflammation · doi:10.1186/s12950-018-0204-9 · Cited by 38
“In OA joint, the activation of innate immune system markedly contributes to an increased expression of inflammatory cytokines, which play a crucial role in the initiation, maintenance, and perpetuation of osteoarthritic cartilage destruction [26, 27].”
BackgroundZhao, X., Li, Y., Lin, X.-W., Wang, J., Zhao, X.-J., Xie, J.-T., Sun, T., & Fu, Z.-J. (2018) · Journal of Pain Research · doi:10.2147/jpr.s183594 · Cited by 38
“Furthermore, these proinflammatory cytokines play important roles in disrupting the cartilaginous metabolic balance between MMPs and TIMPs, which mediate cartilage degradation.(44) These proinflammatory cytokines increase the release of MMPs and aggrecanase, which are enzymes that degrade the matrices, causing cartila…”
BackgroundLevings, R. W., Smith, A. D., Broome, T. A., Rice, B. L., Gibbs, E. P., Myara, D. A., Hyddmark, E. V., Nasri, E., Zarezadeh, A., Levings, P. P., et al. (2018) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.143 · Cited by 50
“While joint injury and traumatic loading are considered initiating factors in OA, a consensus in the literature points to interleukin-1 (IL-1), synthesized locally by chondrocytes and synovial cells, as a central mediator of disease progression.(2,3) Although proteins, such as interleukin-1 receptor”
BackgroundYin, W.-H., & Lei, Y. (2018) · International Immunopharmacology · doi:10.1016/j.intimp.2018.08.035 · Cited by 38
Służalska, K. D., Liebisch, G., Lochnit, G., Ishaque, B. A., Hackstein, H., Schmitz, G., Rickert, M., & Steinmeyer, J. (2017) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2017.07.011 · Cited by 40
Šutovský, J., Benčo, M., Šútovská, M., Kočmálová, M., Pappová, L., Miklušica, J., FRAŇO, A., & Kurča, E. (2017) · International Journal of Surgery · doi:10.1016/j.ijsu.2017.06.024 · Cited by 32
Young, I.-C., Chuang, S.-T., Hsu, C.-H., Sun, Y.-J., Liu, H.-C., Chen, Y.-S., & Lin, F. (2017) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-017-1581-y · Cited by 38
Chang, N., Lin, C.-C., Shie, M., Yeh, M.-L., Li, C.-F., Liang, P., Lee, K.-W., Shen, P.-H., & Chu, C.-J. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.09.026 · Cited by 38
“Therefore, control of a suitable microenvironment that includes the regulation of the synthetic (anabolic) and resorptive (catabolic) cytokines of the chondrocytes plays a critical role in facilitating the healing process for cartilage repair [6].”
InfluentialComblain, F., Sanchez, C., Lesponne, I., Balligand, M., Serisier, S., & Henrotin, Y. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121654 · Cited by 38
“Evidence to date indicates that in addition to IL-1β, IL-6 and IL-8 can also promote articular cartilage extracellular matrix degradation or synergize with other cytokines to amplify and accelerate cartilage destruction [29, 33].”
BackgroundFirst insights into human acetabular labrum cell metabolism.
Dhollander, A., Lambrecht, S., Verdonk, P., Audenaert, E., Almqvist, K., Pattyn, C., Verdonk, R., Elewaut, D., & Verbruggen, G. (2012) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2012.03.023 · Cited by 38
Wei, L.-W., Pan, Q., Teng, J., Zhang, H., & Qin, N. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100884 · Cited by 37
“Both IL-b and TNF-a exhibit catabolic action and perpetuate cartilage matrix degradation in osteoarthritis, including the suppression of type II collagen and activation of proteinase [48,49].”
BackgroundRuan, Q., Wang, C., Zhang, Y., & Sun, J. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110924 · Cited by 37
Role of pro-inflammatory interleukins in osteoarthritis: a narrative review
Jrad, A. I. S., Trad, M., Bzeih, W., Hasbani, G. E., & Uthman, I. W. (2022) · Connective Tissue Research · doi:10.1080/03008207.2022.2157270 · Cited by 39
Félix, F. B., Vago, J. P., Beltrami, V. A., Araújo, J. M. D., Grespan, R., Teixeira, M. M., & Pinho, V. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106246 · Cited by 46
Orhan, C., Juturu, V., Şahin, E., Tuzcu, M., Ozercan, I., Durmuş, A., Şahin, N., & Şahi̇n, K. (2021) · Frontiers in Veterinary Science · doi:10.3389/fvets.2021.617789 · Cited by 37
“Increasing pro-inflammatory cytokines including interleukin 1 β (IL-1β), IL-8, and tumor necrosis factor-alpha (TNF-α) activate the nuclear factor kappa B (NF-κB) pathway that promotes the catabolic process in the joint cartilage via upregulation of matrix metalloproteinases (MMPs) (3).”
BackgroundChen, D., Lu, D., Liu, H.-X., Xue, E., Zhang, Y., Shang, P., & Pan, X.-Y. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.10.054 · Cited by 37
Qiu, W.-J., Xu, M.-M., Zhu, X.-D., & Ji, Y. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.105839 · Cited by 37
Luca, P. D., Colombini, A., Carimati, G., Beggio, M., de Girolamo, L., & Volpi, P. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8070975 · Cited by 37
“For gene expression analysis and cytokine evaluation (ELISA), the cells were treated for 48 hours with 1 mg/mL of CG in the presence or absence of 1 ng/mL of IL-1β.”
BackgroundMethodInfluentialEmerging therapeutic agents in osteoarthritis.
Alcaraz, M., Guillén, M. I., & Ferrándiz, M. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.02.034 · Cited by 37
Gao, F., & Zhang, S.-Y. (2019) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2019.1591427 · Cited by 37
Li, M., Zhao, J.-Q., & Jia, L. (2019) · Life Science · doi:10.1016/j.lfs.2018.12.014 · Cited by 37
Behavioral immune system activity predicts downregulation of chronic basal inflammation
Gassen, J., Prokosch, M. L., Makhanova, A., Eimerbrink, M. J., White, J. D., Leyva, R. P. P., Peterman, J. L., Nicolas, S. C. A., Reynolds, T. A., Maner, J. K., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0203961 · Cited by 41
Grant, A., Letson, H., Morris, J. L., McEwen, P., Hazratwala, K., Wilkinson, M., & Dobson, G. (2018) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-018-0855-5 · Cited by 37
“TNF-α is another potent inflammatory mediator involved in OA progression [36, 37], contributing to cartilage loss through its suppression of collagen and proteoglycan synthesis [24, 36, 38].”
BackgroundPark, J., Yun, Y.-P., Park, K., Lee, J. Y., Kim, H.-J., Kim, S. E., & Song, H.-R. (2016) · Colloids and Surfaces B: Biointerfaces · doi:10.1016/j.colsurfb.2016.07.050 · Cited by 37
Suppression of Cartilage Degradation by Zingerone Involving the p38 and JNK MAPK Signaling Pathway
Ruangsuriya, J., Budprom, P., Viriyakhasem, N., Kongdang, P., Chokchaitaweesuk, C., Sirikaew, N., Chomdej, S., Nganvongpanit, K., & Ongchai, S. (2016) · Planta Medica · doi:10.1055/s-0042-113387 · Cited by 37
“These cytokines are classified as catabolic factors to develop OA, of which the increase in their expression not only magnifies these cytokines themselves in autocrine and paracrine fashions, but also enhances degradative enzymes, such as MMPs and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)…”
BackgroundPapathanasiou, I., Michalitsis, S., Hantes, M., Vlychou, M., Anastasopoulou, L., Malizos, K., & Tsezou, A. (2016) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-016-0871-8 · Cited by 37
“It has been shown that pro-inflammatory cytokines are released in the synovial fluid in patients with acute or chronic ACL injury and are involved in MMPs stimulation and initiation of cartilage degradation [12–15].”
The chemokine CCL20 induces proinflammatory and matrix degradative responses in cartilage
Alaaeddine, N., Antoniou, J., Moussa, M., Hilal, G., Kreichaty, G., Ghanem, I., Abouchedid, W., Saghbini, E., & Battista, J. D. D. (2015) · Inflammation Research · doi:10.1007/s00011-015-0854-5 · Cited by 37
“, inflammatory cytokines, chemokines, lipid mediators, reviewed in [12]).”
BackgroundEndocannabinoids and Acute Pain Following Total Knee Arthroplasty
Azim, S., Nicholson, J., Rebecchi, M., Galbavy, W., Feng, T., Reinsel, R., Volkow, N., Benveniste, H., & Kaczocha, M. (2015) · Pain · doi:10.1097/01.j.pain.0000460315.80981.59 · Cited by 37
“painful OA have been identified including interleukins (eg, IL-6) and prostaglandins.(26,50) The endocannabinoid system has recently emerged as”
BackgroundTsai, S., Huang, Y.-C., Chueh, L., Yeh, L.-S., & Lin, C.-S. (2014) · World journal of transplantation · doi:10.5500/wjt.v4.i3.196 · Cited by 37
Zhang, J., Li, K., & Qiu, X. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1362012 · Cited by 36
Arthritic Microenvironment‐Dictated Fate Decisions for Stem Cells in Cartilage Repair
He, S., Deng, H., Li, P., Hu, J., Yang, Y., Xu, Z., Liu, S., Guo, W., & Guo, Q. (2023) · Advanced Science · doi:10.1002/advs.202207715 · Cited by 36
Dual-functional MOFs-based hybrid microgel advances aqueous lubrication and anti-inflammation.
Wu, W., Liu, J., Lin, X., He, Z., Zhang, H., Ji, L., Gong, P.-W., Zhou, F., & Liu, W.-M. (2023) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2023.04.071 · Cited by 36
Cai, Y., Zhang, G., Liang, J., Jing, Z., Zhang, R., Lv, L., & Dang, X. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.793023 · Cited by 38
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“Biological therapies targeting cytokines hold great promise for the treatment of various diseases (14).”
BackgroundA review of applications of metabolomics in osteoarthritis
Li, J., Zeng, N., Yan, Z., Liao, T., & Ni, G. (2020) · Clinical Rheumatology · doi:10.1007/s10067-020-05511-8 · Cited by 36
“BCAA supplements are associated with the increased production of the main proinflammatory cytokines involved in the pathophysiology of OA, including IL-1 and 2, tumor necrosis factor–alpha, and interferon-gamma [53], which are implicated in the degeneration of the articular cartilage matrix [54].”
BackgroundBiological perspectives and current biofabrication strategies in osteochondral tissue engineering
Vyas, C., Mishbak, H., Cooper, G., Peach, C., Pereira, R., & Bártolo, P. (2020) · Biomanufacturing Reviews · doi:10.1007/s40898-020-00008-y · Cited by 36
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“Proinflammatory cytokines, including TNF-α and IL1β, are well-known to induce OA [9, 10, 13].”
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“For instance, biochemical and biomechanical factors can trigger proinflammatory responses that ultimately lead to articular cartilage destruction in OA [10].”
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“Several pro-inflammatory cytokines have been implicated in the regulation of osteoblasts and osteoclasts, and a shift towards an activated immune profile has been hypothesized to be an important risk factor.(5,6) Studies related to cytokine balance in human osteoporosis are still few in number, and the majority of dat…”
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“Inflammatory molecules, including pro‑inflammatory cytokines, are reported to be important mediators involved in the pathophysiology of OA (5).”
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“Many emerging evidences demonstrate the role of immune responses in the pathogenesis of osteoarthritis [1, 13, 14].”
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Metadata
- Authors
- Kapoor, M., Martel-Pelletier, J., Lajeunesse, D., Pelletier, J.-P., & Fahmi, H.
- Affiliations
- Hôpital Notre-Dame (CA)
- Venue
- Nature Reviews Rheumatology
- Published
- 2010-11-30
- Volume
- 7
- Issue
- 1
- Pages
- 33-42
- ISSN
- 1759-4790 (ISSN-L)
- 1759-4804
- OpenAlex
- W2038773696
- Cited by
- 2,778
- References
- 120
- Citations by year
- 2026: 207 · 2025: 232 · 2024: 252 · 2023: 271 · 2022: 249 · 2021: 252 · 2020: 234 · 2019: 199 · 2018: 175 · 2017: 141 · 2016: 145 · 2015: 128 · 2014: 106 · 2013: 83 · 2012: 73
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Rheumatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Keywords
- osteoarthritis, inflammatory cytokines, IL-1β, TNF-α, interleukin-6, cartilage degeneration, subchondral bone remodeling, synovitis, anti-cytokine therapy, IL-17, IL-18, IL-21, leukemia inhibitory factor, interleukin-8
- MeSH terms
- Cartilage, Articular, Humans, Osteoarthritis, Tumor Necrosis Factor-alpha, Interleukin-6, Disease Progression, Interleukin-1beta
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