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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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USP7 Inhibition Alleviates H2O2-Induced Injury in Chondrocytes via Inhibiting NOX4/NLRP3 Pathway
Liu, G., Liu, Q.-B., Yan, B., Zhu, Z.-Q., & Xu, Y. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.617270 · Cited by 71
“Increasing pieces of evidence show that proinflammatory cytokines participate in OA, and IL-1β and IL-18 play a crucial role in the progression of OA (Kapoor et al., 2011; Ding et al., 2017).”
BackgroundZhou, X.-D., Jiang, L.-F., Fan, G.-M., Yang, H.-Y., Wu, L.-D., Huang, Y., Xu, N.-W., & Li, J. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.03.037 · Cited by 71
Ren, G., Lutz, I., Railton, P., Wiley, J., McAllister, J., Powell, J., & Krawetz, R. (2018) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-018-1955-4 · Cited by 71
“Inflammation is known to be present in OA and the changes in individual inflammatory markers have been correlated with both severity and progression and OA [15, 16].”
BackgroundLee, J., Hong, Y.-O.-S., Jeong, J.-H., Yang, E.-J., Jhun, J., Park, M., Jung, Y., Min, J., Kim, H. Y., Park, S. H., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069362 · Cited by 71
“In concert with IL-1b, IL-6 upregulated MMP-1 and MMP-13 expression in human cartilage extract culture [25].”
BackgroundInfluentialInduction of the chemokine IL-8/Kc by the articular cartilage: possible influence on osteoarthritis.
Chauffier, K., Laiguillon, M.-C., Bougault, C., Gosset, M., Priam, S., Salvat, C., Mladenovic, Z., Nourissat, G., Jacques, C., Houard, X., et al. (2012) · Joint, bone, spine : revue du rhumatisme · doi:10.1016/j.jbspin.2011.12.013 · Cited by 71
“Taking into account their well-known roles in many inflammatory processes, chemokines represent additional key mediators in OA [2].”
BackgroundInfluentialOusema, P., Moutos, F. T., Estes, B., Caplan, A. I., Lennon, D. P., Guilak, F., & Weinberg, J. B. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.08.045 · Cited by 71
An extensive review regarding the adipokines in the pathogenesis and progression of osteoarthritis
Tu, C., He, J., Wu, B., Wang, W., & Li, Z. (2018) · Cytokine · doi:10.1016/j.cyto.2018.06.019 · Cited by 85
Colombini, A., Libonati, F., Lopa, S., Peretti, G., Moretti, M., & Girolamo, L. (2022) · Knee Surgery, Sports Traumatology, Arthroscopy · doi:10.1007/s00167-022-07030-2 · Cited by 70
“Osteoarthritis is characterized by progressive joint destruction [5, 6] due to the alteration of the physiological balance between chondrocyte anabolic and catabolic activities [24], and promote also a hypertrophic phenotype in other joint resident cells [28, 38, 42].”
BackgroundExercise for Osteoarthritis: A Literature Review of Pathology and Mechanism
Kong, H., Wang, X., & Zhang, X. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.854026 · Cited by 82
Jia, S., Yang, Y., Bai, Y., Wei, Y., Zhang, H., Tian, Y., Liu, J., & Bai, L. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.797855 · Cited by 70
“Among the inflammatory cytokines that induce OA, IL-1β has been shown to play a critical role because it contributes to chondrocyte degradation by inducing the expression of MMP13 and ADAMTS-5 during the pathogenesis of OA (Hu et al., 2019; Kapoor et al., 2011).”
BackgroundIntra-articular Injection of Magnesium Chloride Attenuates Osteoarthritis Progression in Rats.
Yao, H., Xu, J.-K., Zheng, N., Wang, J.-L., Mok, S.-W., Lee, Y. W., Shi, L., Wang, J., Yue, J., Yung, S., et al. (2019) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2019.08.007 · Cited by 70
Astaxanthin protects against osteoarthritis via Nrf2: a guardian of cartilage homeostasis
Sun, K., Luo, J.-H., Jing, X.-Z., Guo, J.-C., Yao, X., Hao, X.-X., Ye, Y.-P., Liang, S., Lin, J.-M., Wang, G.-C., et al. (2019) · Aging · doi:10.18632/aging.102474 · Cited by 70
“In addition, TNF-α plays an important role in inducing ROS production and cell apoptosis [6].”
BackgroundInfluentialYang, P., Tan, J.-L., Yuan, Z., Meng, G., Bi, L., & Liu, J. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.08.005 · Cited by 70
Platelet-Rich Plasma Modulates Actions on Articular Cartilage Lubrication and Regeneration
Sakata, R., & Reddi, A. H. (2016) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2015.0534 · Cited by 77
“78,79 Cyclooxygenase-2 (COX2) is well known to stimulate prostaglandin E2 synthesis from arachidonic acid and to have a direct link with the symptomatic treatment with nonsteroidal anti-inflammatory agents (NSAIDs).”
Yang, J., Xiao, S., Deng, J., Li, Y., Hu, H., Wang, J., Lu, C., Li, G., Zheng, L., Wei, Q., et al. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02678-z · Cited by 73
“…chain reaction (qRT-PCR) showed that compared with the normal group, MMP-13, IL-6, tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS) were significantly upregulated, while Col2α1 and aggregated proteoglycan (ACAN) were significantly downregulated in the IL-1β group [48–50].”
BackgroundZou, Z., Hu, W., Kang, F., Xu, Z., Li, Y., Zhang, J., Li, J., Zhang, Y., & Dong, S. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.04.012 · Cited by 69
“Inflammatory mediator IL-1 b serves as a key pathogenic factor of OA under the pro-inflammatory micro environment of osteoarthritic joints [42].”
Chen, Y., Xu, W., Shafiq, M., Song, D., Wang, T., Yuan, Z., Xie, X.-R., Yu, X., Shen, Y., Sun, B.-B., et al. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.11.040 · Cited by 69
Advances in the pharmaceutical treatment options for canine osteoarthritis
Pye, C., Bruniges, N., Peffers, M., & Comerford, E. (2022) · Journal of Small Animal Practice · doi:10.1111/jsap.13495 · Cited by 69
Wang, Y.-J., Shen, S., Li, Z., Li, W., & Weng, X. (2019) · Inflammation Research · doi:10.1007/s00011-019-01294-0 · Cited by 69
Scotece, M., Conde, J., Abella, V., López, V., Francisco, V., Ruiz‐Fernández, C., Campos, V. M., Lago, F., Gómez, R., Pino, J., et al. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000493840 · Cited by 78
Do immune cells lead the way in subchondral bone disturbance in osteoarthritis?
Weber, A., Chan, P. M., & Wen, C. (2017) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2017.12.004 · Cited by 77
Chen, C., Zhang, C., Cai, L., Xie, H., Hu, W., Wang, T., Lu, D., & Chen, H. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.09.017 · Cited by 69
Askari, A., Naghizadeh, M., Homayounfar, R., Shahi, A., Afsarian, M. H., Paknahad, A., Kennedy, D., & Ataollahi, M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0164757 · Cited by 69
Martel-Pelletier, J., Raynauld, J.-P., Dorais, M., Abram, F., & Pelletier, J.-P. (2016) · Rheumatology · doi:10.1093/rheumatology/kev408 · Cited by 68
Self-citationHe, L., Pan, Y.-F., Yu, J.-P., Wang, B., Dai, G., & Ying, X. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107657 · Cited by 68
Li, L., Lv, G.-H., Wang, B., & Kuang, L. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.28968 · Cited by 68
Park, M.-J., Moon, S.-J., Baek, J.-A., Lee, E.-J., Jung, K., Kim, E.-K., Kim, D.-S., Lee, J.-H., Kwok, S.-K., Min, J., et al. (2019) · Journal of Immunology · doi:10.4049/jimmunol.1800006 · Cited by 68
Brunger, J. M., Zutshi, A., Willard, V. P., Gersbach, C. A., & Guilak, F. (2016) · Arthritis & Rheumatology · doi:10.1002/art.39982 · Cited by 66
“Nitric oxide and PGE2 were assayed using commercially available kits (R&D Systems) following the manufacturer’s instructions.”
BackgroundInfluentialRecent development of mitochondrial metabolism and dysfunction in osteoarthritis
Guo, P., Alhaskawi, A., Moqbel, S. A. A., & Pan, Z. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1538662 · Cited by 52
Yang, S.-Y., Sun, M., & Zhang, X. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.921003 · Cited by 67
“Studies show that under pathological conditions of KOA, chondrocytes and synoviocytes overexpress inflammatory factors, such as interleukin-1β (IL-1β), cyclooxygenase 2(COX2), and tumor necrosis factor-α (TNF-α), to hasten cartilage degeneration (Kapoor et al., 2011).”
BackgroundInsight into the roles of melatonin in bone tissue and bone‑related diseases (Review)
Lu, X., Yu, S., Chen, G., Zheng, W., Peng, J., Huang, X., & Chen, L. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.4915 · Cited by 94
“OA, inducing chondrocyte metabolic disorders and cartilage dysfunction, ultimately resulting in joint dysfunction (76,77).”
BackgroundWatkins, L. R., Chavez, R. A., Landry, R., Fry, M., Green‐Fulgham, S. M., Coulson, J. D., Collins, S. D., Glover, D. K., Rieger, J. M., & Forsayeth, J. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.08.005 · Cited by 67
Ziadlou, R., Barbero, A., Martín, I., Wang, X., Qin, L., Alini, M., & Grad, S. (2020) · Biomolecules · doi:10.3390/biom10060932 · Cited by 73
“Previous studies have reported that interleukin 1β (IL1-β) and tumor necrosis factor α (TNF-α) are the main pro-inflammatory cytokines initiating inflammation and causing matrix degradation in OA [5,6].”
ResultKwon, J., Lee, S.-H., Na, H., Jung, K., Choi, J., Cho, K.-H., Lee, C.-Y., Kim, S., Park, S.-H., Shin, D.-Y., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-32206-7 · Cited by 67
Wang, J.-P. (2017) · Journal of International Medical Research · doi:10.1177/0300060517723182 · Cited by 67
“It increases sharply in the acute phase of knee OA and is responsible for driving the development and severity of inflammation.11 Several in vitro and in vivo studies have revealed that TNF-a also acts as a mediator for the activity of NGF expression, which causes neuropathic pain in patients with OA.12,17 Additionall…”
BackgroundInfluentialHuang, Z.-M., Du, S.-H., Huang, L.-G., Li, J.-H., Xiao, L.-W., & Tong, P. (2016) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2016.02.009 · Cited by 67
CCL3/CCR1 mediates CD14+CD16− circulating monocyte recruitment in knee osteoarthritis progression
Zhao, X., Gu, M., Xu, X., Wen, X., Yang, G., Li, L., Sheng, P., & Meng, F. (2020) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2020.01.009 · Cited by 66
Microenvironment-responsive nanocarriers for targeted bone disease therapy
Li, M., Yu, B., Wang, S., Zhou, F., Cui, J., & Su, J. (2023) · Nano Today · doi:10.1016/j.nantod.2023.101838 · Cited by 70
Rhoifolin ameliorates osteoarthritis via the Nrf2/NF-κB axis: in vitro and in vivo experiments.
Chen, H., Qin, J., Shi, H.-S., Li, Q., Zhou, S.-Q., & Chen, L.-B. (2022) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2022.01.009 · Cited by 66
Na, H. S., Kwon, J. Y., Lee, S.-Y., Lee, S., Lee, A. R., Woo, J. S., Jung, K., Cho, K.-H., Choi, J., Lee, D. H., et al. (2021) · Cells · doi:10.3390/cells10030681 · Cited by 67
“Targeting these proinflammatory cytokines has thus emerged as a therapeutic option in OA [4].”
BackgroundSong, J., Baek, I.-J., Chun, C.-H., & Jin, E.-J. (2018) · Nature Communications · doi:10.1038/s41467-018-05787-0 · Cited by 66
Jiang, Y.-Z., Cai, Y.-Z., Zhang, W., Yin, Z., Hu, C., Tong, T., Lu, P., Zhang, S., Neculai, D., Tuan, R., et al. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0192 · Cited by 66
Nummenmaa, E., Hämäläinen, M., Moilanen, L. J., Paukkeri, E.-L., Nieminen, R., Moilanen, T., Vuolteenaho, K., & Moilanen, E. (2016) · Arthritis Research & Therapy · doi:10.1186/s13075-016-1080-4 · Cited by 66
“In part IL-17 feeds forward these mechanisms as it further induces IL-1β, TNF, and IL-6 production, upregulates NO and MMPs and downregulates proteoglycan levels related to the pathogenesis of OA [28].”
BackgroundInfluentialLiu, S., Lee, H., Hung, C.-Y., Tsai, C., Li, T., & Tang, C. (2015) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2015.08.020 · Cited by 65
Ni, S., Miao, K.-S., Zhou, X.-J., Xu, N.-W., Li, C., Zhu, R., Sun, R.-B., & Wang, Y.-J. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0605-6 · Cited by 66
“TNF-α, IL-1β and IL-6 are thought to be the key proinflammatory cytokines related to the pathophysiology of OA [33].”
BackgroundGut microbiome dysbiosis alleviates the progression of osteoarthritis in mice
Guan, Z., Jia, J., Zhang, C., Sun, T., Zhang, W., Yuan, W., Leng, H., & Song, C. (2020) · Clinical Science · doi:10.1042/cs20201224 · Cited by 81
Na, H. S., Park, J., Cho, K.-H., Kwon, J. Y., Choi, J., Jhun, J., Kim, S. J., Park, S., & Cho, M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00730 · Cited by 73
“IL-17, which is mainly produced in Th17 cells, promotes cartilage degradation by promoting MMPs, Frontiers in Immunology | www.frontiersin.org 7 May 2020 | Volume 11 | Article 730 Frontiers in Immunology | www.frontiersin.org 8 May 2020 | Volume 11 | Article 730 disintegrin, and metalloproteinase, with thrombospondin…”
BackgroundInfluentialHou, S.-M., Chen, P.-C., Lin, C.-M., Fang, M.-L., Chi, M.-C., & Liu, J.-F. (2020) · Arthritis Research & Therapy · doi:10.1186/s13075-020-02331-8 · Cited by 65
Lei, J.-L., Fu, Y.-H., Zhuang, Y., Zhang, K., & Lu, D.-G. (2019) · Bioscience Reports · doi:10.1042/bsr20191523 · Cited by 65
Huang, S., Song, X.-B., Li, T., Xiao, J., Chen, Y., Gong, X., Zeng, W.-N., Yang, L., & Chen, C. (2017) · Stem cell research & therapeutics · doi:10.1186/s13287-017-0719-7 · Cited by 65
“Here, we examined the concentration of IL-1β (a major cytokine in OA [39]), ADAMTS 5 (an enzyme responsible for aggrecan degradation [40]), and MMP-13 (an enzyme responsible for collagen degradation [41]) during coculture.”
BackgroundRhee, J., Park, S.-H., Kim, S., Kim, J.-H., Ha, C., Chun, C.-H., & Chun, J.-S. (2016) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2015-208953 · Cited by 65
Yang, M., Ding, J., Zhang, Y., Chang, F., Wang, J., Gao, Z., Zhuang, X., & Chen, X. (2016) · Journal of Materials Chemistry B · doi:10.1039/c5tb02479j · Cited by 83
Akhtar, N., Makki, M., & Haqqi, T. (2015) · Arthritis & Rheumatology · doi:10.1002/art.38952 · Cited by 65
“IL-1 is a key player in the pathogenesis of OA (3,40) and up-regulates MMP-13 expression in cartilage (41).”
BackgroundAssirelli, E., Pulsatelli, L., Dolzani, P., Platano, D., Olivotto, E., Filardo, G., Trisolino, G., Facchini, A., Borzì, R., & Meliconi, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096925 · Cited by 65
“Among several potential inflammatory/catabolic mediators, chemokines were selected because of their relevance in OA pathophysiology [2,24] and because, due to their small size, they can greatly contribute to the crosstalk between joint compartments (cartilage, synovium and subchondral bone) [25].”
BackgroundCheleschi, S., Tenti, S., Seccafico, I., Gálvez, I., Fioravanti, A., & Ortega, E. (2021) · Environmental science and pollution research international · doi:10.1007/s11356-021-17780-0 · Cited by 64
Wang, Y.-J., Cui, J., Gu, Z.-R., Fang, C., Hu, Y., Weng, W., Li, X.-Q., Zhou, Q.-R., Chen, H., Zhang, H., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.723988 · Cited by 64
“Osteoarthritis is considered a whole-joint disease characterized by articular cartilage deterioration, subchondral bone edema and sclerosis, abnormal angiogenesis and osteophyte formation (Kapoor et al., 2011; Goldring, 2012).”
BackgroundMeta-Analysis of Adipose Tissue Derived Cell-Based Therapy for the Treatment of Knee Osteoarthritis
Agarwal, N., Mak, C., Bojanic, C., To, K., & Khan, W. (2021) · Cells · doi:10.3390/cells10061365 · Cited by 64
“OA pathogenesis is predominantly driven by inflammatory mediators such as interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF-α) [16].”
BackgroundIntra-articular Injection of Chitosan-Based Supramolecular Hydrogel for Osteoarthritis Treatment
Mou, D., Yu, Q., Zhang, J., Zhou, J., Li, X., Zhuang, W., & Yang, X. (2021) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-020-00322-z · Cited by 64
“Furthermore, IL-6 plays a role in the inflammation and degeneration of the knee joint, and causes disorder in subchondral bone metabolism and inhibits the expression of collagen [29].”
BackgroundCurrent Nanoparticle-Based Technologies for Osteoarthritis Therapy
Jin, G.-Z. (2020) · Nanomaterials · doi:10.3390/nano10122368 · Cited by 64
“, IL-1β, IL-6, and TNF-α) secreted by chondrocytes and synovial cells in synovial fluid are critical mediators in OA development [15].”
BackgroundLi, Z., Cheng, J., & Liu, J. (2020) · Drug Design Development and Therapy · doi:10.2147/dddt.s255823 · Cited by 69
Zeng, L., Rong, X.-F., Li, R.-H., & Wu, X.-Y. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6312 · Cited by 64
“Numerous complex pathways and mechanisms are involved in ECM degradation (5).”
BackgroundSiebuhr, A., Bay-Jensen, A., Jordan, J., Kjelgaard-Petersen, C., Christiansen, C., Abramson, S., Attur, M., Berenbaum, F., Kraus, V., & Karsdal, M. (2016) · Scandinavian Journal of Rheumatology · doi:10.3109/03009742.2015.1060259 · Cited by 64
“The synovium in OA has been shown to contain elevated levels of the pro-inflammatory cytokines IL-1β and TNF-α compared to healthy synovium (38, 52).”
BackgroundInfluentialGlycolysis: an emerging regulator of osteoarthritis
Jiang, D., Guo, J., Liu, Y., Li, W., & Lu, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1327852 · Cited by 59
The role of apoptosis in the pathogenesis of osteoarthritis
Xiao, S.-Q., Miao, C., Wang, L., Cao, J., Fang, L., Zhou, X., He, X.-J., & Hu, Y. (2023) · International Orthopaedics · doi:10.1007/s00264-023-05847-1 · Cited by 68
“A number of studies have suggested the activation of NF-κB, triggering a cascade of events in chondrocytes including the release of inflammatory cytokines and chemokines, such as TNF-α, IL-1β, and IL-6, that increase the secretion of MMPs, reduce production of collagen and proteoglycan, and act in a positive feedback…”
BackgroundLiang, S., Lv, Z., Zhang, J., Wang, Y., Dong, Y., Wang, Z., Chen, K., Cheng, P., Yang, Q., Guo, F., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01378 · Cited by 66
The Disease-Modifying Effects of Hyaluronan in the Osteoarthritic Disease State
Nicholls, M. A., Fierlinger, A. L., Niazi, F., & Bhandari, M. (2017) · Clinical Medicine Insights Arthritis and Musculoskeletal Disorders · doi:10.1177/1179544117723611 · Cited by 67
Chang, J. C., Sebastian, A., Murugesh, D., Hatsell, S., Economides, A., Christiansen, B., & Loots, G. (2016) · Journal of Orthopaedic Research · doi:10.1002/jor.23263 · Cited by 63
“Though OA is commonly diagnosed by visible damage to the articular cartilage, more recent assessments of OA have been migrating to evaluate the entire joint, and perceive the disease as a multi factorial, multi cell-type phenotype.(14,15) In this study, we used a non-invasive tibial compression (TC) mouse model that c…”
Väänänen, T., Koskinen, A., Paukkeri, E., Hämäläinen, M., Moilanen, T. P. S., Moilanen, E., & Vuolteenaho, K. (2014) · Mediators of Inflammation · doi:10.1155/2014/215140 · Cited by 67
Calamia, V., Lourido, L., Fernández‐Puente, P., Mateos, J., Rocha, B., Montell, E., Vergés, J., Ruíz‐Romero, C., & Blanco, F. J. (2012) · Arthritis Research & Therapy · doi:10.1186/ar4040 · Cited by 64
“Inflammatory molecules, such as proinflammatory cytokines, are critical mediators of the disturbed metabolism and enhance the catabolism of joint tissue involved in OA pathophysiology [21].”
BackgroundFan, A.-Y., Wu, G.-B., Wang, J., Lu, L., Wang, J.-Y., Wei, H., Sun, Y., Xu, Y.-H., Mo, C., Zhang, X., et al. (2023) · Bone Research · doi:10.1038/s41413-022-00243-8 · Cited by 62
Wu, Z., Yuan, K., Zhang, Q., Guo, J. J., Yang, H., & Zhou, F. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01697-y · Cited by 68
“Aetiology of OA is multifactorial and remains to be further investigated [9].”
BackgroundShi, X.-Q., Jie, L.-S., Wu, P., Zhang, N.-S., Mao, J., Wang, P.-M., & Yin, S.-J. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.115536 · Cited by 62
miR-10a-5p Promotes Chondrocyte Apoptosis in Osteoarthritis by Targeting HOXA1
Ma, Y., Wu, Y., Chen, J.-X., Huang, K., Ji, B., Chen, Z.-J., Wang, Q., Ma, J.-J., Shen, S., & Zhang, J.-F. (2018) · Molecular Therapy: Nucleic Acids · doi:10.1016/j.omtn.2018.12.012 · Cited by 62
“Millions of people worldwide are affected by OA each year.1 Its symptoms typically include the degradation of articular cartilage, synovitis, chondrocyte apoptosis, inflammation, and the remodeling of subchondral bone.2 Obesity, mechanical stress, genetic predisposition, gender, and aging are key factors in the develo…”
BackgroundInfluentialAllam, G. A., Mahdi, E. A., Alzahrani, A. M., & Abuelsaad, A. S. A. (2017) · Central European Journal of Immunology · doi:10.5114/ceji.2016.65132 · Cited by 65
“leukocyte infiltration, cytokine networks formation, cartilage catabolism elevation, and anabolism suppression [7, 55-58].”
BackgroundJeong, J.-H., Moon, S.-J., Jhun, J., Yang, E.-J., Cho, M., & Min, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0130882 · Cited by 62
“Although the pathophysiology of OA remains poorly understood, inflammatory cytokines, such as IL-1β, IL-6, and IL-17, are all strongly associated with the disruption of homeostasis of ECM components seen in OA pathogenesis [6].”
BackgroundAssociation of chemerin levels in synovial fluid with the severity of knee osteoarthritis
Huang, K., Du, G., Li, L., Liang, H.-S., & Zhang, B. (2012) · Biomarkers · doi:10.3109/1354750x.2011.634028 · Cited by 62
“These inflammatory cytokines were demonstrated to promote pathological OA (Kapoor et al. 2011).”
BackgroundSalvatore, L., Natali, M. L., Brunetti, C., Sannino, A., & Gallo, N. (2023) · Polymers · doi:10.3390/polym15041020 · Cited by 71
“Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 seem to be the main proinflammatory cytokines involved in the pathophysiology of osteoarthritis, even though others, including IL-15, IL-18, IL-21, leukemia inhibitory factor (LIF), and chemokines are implicated [182,219].”
BackgroundRuan, G., Xu, J., Wang, K., Wu, J., Zhu, Q., Ren, J., Bian, F., Chang, B., Bai, X., Han, W., et al. (2018) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2018.05.003 · Cited by 61
Liu, Y.-X., Wang, G.-D., Wang, X., Zhang, Y.-L., & Zhang, T.-L. (2017) · OncoTarget · doi:10.18632/oncotarget.16199 · Cited by 61
“Compared with the control group, increased expressions of TLR-2, NF-κB, phosphorylated-NF-κB (p-NF-κB), MMP-13, IL-1, IL-6 and TNF-α were found in the IL-1β group.”
BackgroundInfluentialEpigenetic regulation of gene expression in osteoarthritis
Zhang, M., & Wang, J. (2015) · Genes & Diseases · doi:10.1016/j.gendis.2014.12.005 · Cited by 63
Sun, J.-M., Sun, L., Liu, J., Su, B., & Shi, L. (2013) · Disease Markers · doi:10.1155/2013/176278 · Cited by 61
The emerging roles of HTRA1 in musculoskeletal disease.
Tiaden, A., & Richards, P. J. (2013) · American Journal of Pathology · doi:10.1016/j.ajpath.2013.02.003 · Cited by 61
“Originally considered to be a noninflammatory disorder, OA has since been associated with a low-level inflammatory response.(17) It has been speculated that inflammation brought about through joint trauma may in fact be one of the main instigators of OA.”
BackgroundYang, H., Zhou, Y.-Q., Ying, B., Dong, X., Qian, Q., & Gao, S.-R. (2024) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szae031 · Cited by 60
Matrix metalloproteinases in rheumatoid arthritis and osteoarthritis: a state of the art review
Pulik, Ł., Łęgosz, P., & Motyl, G. (2023) · Reumatologia/Rheumatology · doi:10.5114/reum/168503 · Cited by 71
Peripheral brain-derived neurotrophic factor contributes to chronic osteoarthritis joint pain
Gowler, P. R. W., Li, L., Woodhams, S. G., Bennett, A. J., Suzuki, R., Walsh, D. A., & Chapman, V. (2019) · Pain · doi:10.1097/j.pain.0000000000001694 · Cited by 64
Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models
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“It is known that TNFα plays an important role in OA [32].”
BackgroundZheng, W., Tao, Z., Cai, L., Chen, C., Zhang, C., Wang, Q., Ying, X., Hu, W., & Chen, H. (2017) · Inflammation · doi:10.1007/s10753-017-0558-9 · Cited by 60
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“Proinflammatory cytokines such as IL-6, TNF-α, and IFN-β are usually induced by oxidant stress, cytokines, and virus infection, which play important roles in host cell damages, chronic inflammation, and other immunoresponses [45-49].”
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“This thereby increases the release and expression of matrix degradative enzymes P-1, P-9, MMP-13, ADAMTS4, and ADAMTS5 [43].”
BackgroundInfluentialThe Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut?
Ramires, L. C., Santos, G. S., Ramires, R. P., da Fonseca, L. F., Jeyaraman, M., Muthu, S., Lana, A. V. S. D., Azzini, G. O. M., Smith, C. S., & Lana, J. F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031494 · Cited by 74
“Cytokines related to OA pathogenesis include tumor necrosis factor (TNF)-α, matrix metalloproteinases (MMPs), interleukin (IL)-1, IL-6, IL-2, IL-7, IL-15 and IL-21, and other chemokines which contribute to catabolic activity and detrimental effects [11,12].”
BackgroundEpigenetic Mechanisms Underlying the Aging of Articular Cartilage and Osteoarthritis
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Ansari, M. Y., Ahmad, N., & Haqqi, T. M. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000493225 · Cited by 62
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“It was reported that inflammatory cytokines participated in the pathogenesis of OA [17,18].”
BackgroundThe role of progranulin in arthritis
Wei, J.-L., Hettinghouse, A., & Liu, C.-J. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13191 · Cited by 59
CCL3 serves as a potential plasma biomarker in knee degeneration (osteoarthritis)
Zhao, X., Yang, Z.-S., Zhang, Z. J., Zhang, Z. Q., Kang, Y. Q., Huang, G. X., Wang, S.-H., Huang, H., & Liao, W. (2015) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2015.04.002 · Cited by 62
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Osteoarthritis: Trauma vs Disease.
Jiménez, G., Cobo-Molinos, J., Antich, C., & López-Ruiz, E. (2018) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-76735-2_3 · Cited by 59
SOST/Sclerostin improves posttraumatic osteoarthritis and inhibits MMP2/3 expression after injury
Chang, J. C., Christiansen, B. A., Murugesh, D. K., Sebastian, A., Hum, N. R., Collette, N. M., Hatsell, S., Economides, A. N., Blanchette, C. D., & Loots, G. G. (2018) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3397 · Cited by 58
“Because Wnt ligands have been shown to increase the expression of MMPs in the human synovium as well as to stimulate the chondrocyte metabolic action in rabbit models of OA,((31)) we propose a mechanism by which joint injury triggers the secretion of IL1, IL-6, and TNFa by immune cells; these cytokines”
BackgroundInfluential
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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