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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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Recent Advances in Animal Models, Diagnosis, and Treatment of Temporomandibular Joint Osteoarthritis
Wang, D., Qi, Y., Wang, Z., Guo, A., Xu, Y., & Zhang, Y. (2022) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2022.0065 · Cited by 61
Yabas, M., Orhan, C., Er, B., Tuzcu, M., Durmuş, A., Ozercan, I., Şahin, N., Bhanuse, P., Morde, A. A., Padigaru, M., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.609629 · Cited by 58
“OA is associated with dysregulated immune mediators (51) with increased levels of pro-inflammatory mediators that play a critical role in the pathophysiology of the disease (52).”
BackgroundZhao, W., Wang, H., Wang, H., Han, Y., Zheng, Z., Liu, X., Feng, B., & Zhang, H. (2021) · Nanoscale · doi:10.1039/d0nr08887k · Cited by 100
Aberrant subchondral osteoblastic metabolism modifies NaV1.8 for osteoarthritis
Zhu, J., Zhen, G., An, S., Wang, X., Wan, M., Li, Y., Chen, Z., Guan, Y., Dong, X., Hu, Y., et al. (2020) · eLife · doi:10.7554/elife.57656 · Cited by 66
Yu, H., Liang, X., Chen, P., Wu, X., Zheng, Y., Luo, L., Qin, Y., Long, X., & Xue, M. (2018) · Aquaculture · doi:10.1016/j.aquaculture.2018.10.033 · Cited by 60
IL-6 in Osteoarthritis: Effects of Pine Stilbenoids
Laavola, M., Leppänen, T., Hämäläinen, M., Vuolteenaho, K., Moilanen, T., Nieminen, R., & Moilanen, E. (2018) · Molecules · doi:10.3390/molecules24010109 · Cited by 58
“IL-1β and IL-17 decreased the synthesis of the two anabolic factors in OA chondrocytes (Figure 5), as expected [12].”
BackgroundMarouf, B. H., Hussain, S., Ali, Z. S., & Ahmmad, R. (2018) · Journal of Medicinal Food · doi:10.1089/jmf.2017.4176 · Cited by 58
Zhang, L., Ma, S., Su, H., & Cheng, J. (2018) · Molecular Therapy: Methods & Clinical Development · doi:10.1016/j.omtm.2018.02.006 · Cited by 58
Zheng, X., Zhao, F.-C., Pang, Y., Li, D.-Y., Yao, S.-C., Sun, S.-S., & Guo, K.-J. (2017) · Journal of molecular medicine · doi:10.1007/s00109-017-1516-6 · Cited by 58
“On the other hand, IL1β strongly inhibits the expression of cartilage-specific genes, such as collagen type II and aggrecan, and thus causes the insufficient synthesis of chondrocyte ECM [9, 10].”
BackgroundNummenmaa, E., Hämäläinen, M., Moilanen, T., Vuolteenaho, K., & Moilanen, E. (2015) · Scandinavian Journal of Rheumatology · doi:10.3109/03009742.2014.1000372 · Cited by 58
“It is a slowly progressing inflammatory disease of the joints, and involves cartilage degradation, synovial inflammation, and subchondral bone remodelling (16, 17).”
BackgroundChen, C., Xie, J., Rajappa, R., Deng, L.-H., Fredberg, J., & Yang, L. (2015) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmu116 · Cited by 58
“Nevertheless, much evidence has revealed that interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are the main proinflammatory cytokines involved in the pathophysiology of OA [2,3].”
BackgroundBowles, R. D., Mata, B. A., Bell, R. D., Mwangi, T. K., Huebner, J., Kraus, V., & Setton, L. (2014) · Arthritis & Rheumatology · doi:10.1002/art.38279 · Cited by 58
“Elevated levels of these proinflammatory cytokines have been observed in OA patients (6,9,10), while TNF and IL-1 antagonism may lead to substantial reductions in pain scores in patients presenting with an inflammatory component of OA (11–13).”
Emerging role and function of Hippo-YAP/TAZ signaling pathway in musculoskeletal disorders
Han, J., Zhang, J., Zhang, X., Luo, W., Liu, L., Zhu, Y., Liu, Q., & Zhang, X. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-04011-9 · Cited by 59
“…tumour necrosis factor-α (TNF-α), interleukin-1β(IL-1β),and Interleukin 6 (IL-6), primarily activate the NF-κB pathway leading to upregulation of matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs), thereby inducing ECM degradation [69–71].”
BackgroundTryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis
Das, N., de Almeida, L. G. N., Derakhshani, A., Young, D. W., Mehdinejadiani, K., SALO, P. T., Rezansoff, A., Jay, G. D., Sommerhoff, C. P., Schmidt, T. A., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37598-3 · Cited by 69
Jin, Y., Zhang, Q., Qin, X., Liu, Z., Li, Z., Zhong, X., Xia, L., He, J., & Fang, B. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01681-6 · Cited by 64
“It was reported that IL-1β is a major pro-inflammatory cytokine in OA and could induce severe inflammatory reactions and cartilage matrix degradation [40, 41].”
BackgroundZhang, H., Zheng, W., Du, L., & Zheng, J. (2021) · Cartilage · doi:10.1177/19476035211023550 · Cited by 70
Buhrmann, C., Popper, B., Aggarwal, B. B., & Shakibaei, M. (2020) · Cell and Tissue Research · doi:10.1007/s00441-020-03188-8 · Cited by 58
“…has been demonstrated that pivotal proinflammatory cytokines, like TNF-α, amplify the pathophysiology of OA and RA and suppression of these cytokines with an antibody is a successful therapeutic target for patients with OA and RA (Gartlehner et al. 2006; Hochberg et al. 2005; Kapoor et al. 2011).”
Cheleschi, S., de Palma, A., Pascarelli, N., Giordano, N., Galeazzi, M., Tenti, S., & Fioravanti, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122660 · Cited by 57
“The release of reactive oxygen species (ROS), such as superoxide anion, hydrogen peroxide (H2O2) and nitric oxide, contributes to cartilage damage and a concomitant low-grade chronic inflammation [3].”
BackgroundSun, W., Li, Y.-T., & Wei, S. (2017) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2017.5444 · Cited by 57
“It was well-known that TNF-α played a vital role in the pathogenesis of OA, and participated in the progression of cartilage degeneration (29).”
Akhtar, N., Khan, N. M., Ashruf, O. S., & Haqqi, T. (2016) · Nutrition (Burbank, Los Angeles County, Calif.) · doi:10.1016/j.nut.2016.08.004 · Cited by 57
Guzman, N. A., & Phillips, T. M. (2011) · Electrophoresis · doi:10.1002/elps.201000700 · Cited by 60
Shi, T.-F., Zhao, J.-T., Long, K., Gao, M., Chen, F.-M., Chen, X.-N., Zhang, Y., Huang, B.-D., Shao, D., Yang, C., et al. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122366 · Cited by 56
Gandhi, Y., Kumar, R. A., Grewal, J., Rawat, H., Mishra, S. K., Kumar, V. L., Shakya, S. K., Jain, V., Babu, G., Sharma, P., et al. (2022) · Food Chemistry Advances · doi:10.1016/j.focha.2022.100085 · Cited by 71
Valentino, A., Conte, R., Luca, I. D., Cristo, F. D., Peluso, G., Bosetti, M., & Calarco, A. (2022) · Antioxidants · doi:10.3390/antiox11061210 · Cited by 56
“Increases in the levels of the cytokines in joints plays a central role in the pathogenesis of OA by modulating oxidative stress, cartilage ECM turnover, and chondrocytes apoptosis [62,63].”
BackgroundRole of OSCAR Signaling in Osteoclastogenesis and Bone Disease
Nedeva, I. R., Vitale, M., Elson, A., Hoyland, J. A., & Bella, J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.641162 · Cited by 72
Chen, Z.-J., Zhang, F., Zhang, H.-B., Cheng, L., Chen, K., Shen, J., Qi, J., Deng, L., He, C., Santos, H., et al. (2021) · Advancement of science · doi:10.1002/advs.202004793 · Cited by 56
Cordaro, M., Siracusa, R., Impellizzeri, D., D’Amico, R., Peritore, A. F., Crupi, R., Gugliandolo, E., Fusco, R., Paola, R. D., Schievano, C., et al. (2019) · Arthritis Research & Therapy · doi:10.1186/s13075-019-2048-y · Cited by 58
Hu, S., Mao, G., Zhang, Z., Wu, P., Wen, X., Liao, W., & Zhang, Z. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.05.011 · Cited by 63
Shkhyan, R., Handel, B. V., Bogdanov, J. M., Lee, S., Yu, Y., Scheinberg, M., Banks, N. W., Limfat, S., Chernostrik, A., Franciozi, C. E. D. S., et al. (2018) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2017-212037 · Cited by 60
Santos-Savio, A., Diaz, A. C. M., Chico-Capote, A., Miranda-Navarro, J., Alvarez, Y. R., Bringas-Pérez, R., del Toro, M. E., & Nieto, G. G. G. (2015) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-015-0516-3 · Cited by 56
“Biological onset of OA is not clearly understood but evidence suggests that progression of cartilage degradation is mediated largely by proinflammatory cytokines [31,32].”
BackgroundAudette, R., Lavoie-Lamoureux, A., Lavoie, J., & Laverty, S. (2013) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2013.05.004 · Cited by 56
Mei, Z., Yilamu, K., Ni, W., Shen, P., Pan, N., Chen, H., Su, Y., Guo, L., Sun, Q., Li, Z., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60037-4 · Cited by 63
Wang, L., Xu, H., Li, X., Chen, H., Zhang, H.-G., Zhu, X., Lin, Z., Guo, S.-Y., Bao, Z., Rui, H.-C., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04771-7 · Cited by 55
“Studies have shown that persistent inflammation and ECM degradation promote the development of osteoarthritis [36].”
BackgroundIL-17 in osteoarthritis: A narrative review
Xiao, J., Zhang, P., Cai, F.-L., Luo, C., Pu, T., Pan, X.-L., & Tian, M. (2023) · Open Life Sciences · doi:10.1515/biol-2022-0747 · Cited by 47
BNIP3-Dependent Mitophagy via PGC1α Promotes Cartilage Degradation
Kim, D., Song, J., & Jin, E. (2021) · Cells · doi:10.3390/cells10071839 · Cited by 56
“The pathogenesis of OA is characterized by extracellular matrix (ECM) degradation and cellular stress that lead to the activation of proinflammatory cytokines [2,3] or dysfunction of cellular organelles such as endoplasmic reticulum (ER) [4,5], peroxisome [6,7], and mitochondria [8–10].”
BackgroundLi, T., Yang, J.-J., Weng, C., Liu, P., Huang, Y., Meng, S., Li, R., Yang, L., Chen, C., & Gong, X. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.12.158 · Cited by 55
Wang, P., Meng, Q., Wang, W., Zhang, S., Xiong, X., Qin, S., Zhang, J., Li, A., & Liu, Z. (2020) · Bioscience Reports · doi:10.1042/bsr20203107 · Cited by 61
Wu, Y., Wang, Z., Fu, X., Lin, Z., & Yu, K.-H. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106713 · Cited by 55
Luca, P. D., Kouroupis, D., Viganò, M., Perucca-Orfei, C., Kaplan, L., Zagra, L., de Girolamo, L., Correa, D., & Colombini, A. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8040423 · Cited by 55
“A limitation of the present study is that only one in vitro model of inflammation was tested; nevertheless, IL-1β was chosen because it is the most used agent to induce in vitro inflammation to mimic OA [31,32].”
MethodShan, Y., Qi, C., Liu, Y., Gao, H., Zhao, D., & Jiang, Y.-F. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6132 · Cited by 55
“Previous studies have reported elevated IL‑21 levels and transcription product in the synovial fluid of both early-and advanced-stage knee OA (23,24).”
Bauer, C., Niculescu-Morzsa, E., Jeyakumar, V., Kern, D., Späth, S., & Nehrer, S. (2016) · Journal of Inflammation · doi:10.1186/s12950-016-0139-y · Cited by 55
An update on the up and coming therapies to treat osteoarthritis, a multifaceted disease
Roman-Blas, J., Bizzi, E., Largo, R., Migliore, A., & Herrero-Beaumont, G. (2016) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2016.1201070 · Cited by 55
Jiang, Y.-Z., Hu, C., Yu, S., Yan, J.-W., Peng, H., Ouyang, H.-W., & Tuan, R. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0840-x · Cited by 55
“Representative sample is shown (n= 3). c Early-passage cells isolated from healthy cartilage (passage 1 (P1); n= 3, biological replicates, mean ± SD) and late passage from OA articular cartilage (passage 4 (P4); n= 5, biological replicates, mean ± SD) are not chemotactic for NGF (10 ng/ml), p >0.05. d CSPC proliferati…”
BackgroundInfluentialWillard, V. P., Diekman, B. O., Sanchez‐Adams, J., Christoforou, N., Leong, K. W., & Guilak, F. (2014) · Arthritis & Rheumatology · doi:10.1002/art.38780 · Cited by 51
“The pathogenesis of OA and the loss of cartilage homeostasis are dependent in part on the action of inflammatory cytokines, such as interleukin-1 (IL-1) (6,7), that also mediate the production of proinflammatory mediators (i.”
BackgroundThe Treatment of Joint Pain with Intra-articular Pulsed Radiofrequency
Schianchi, P., Sluijter, M., & Balogh, S. E. (2013) · Anesthesiology and Pain Medicine · doi:10.5812/aapm.10259 · Cited by 55
“Experimental data have shown that OA is a result of an episode of mild inflammatory processes within the joint (16) that lead to high levels of pro-inflammatory cytokines (8-10, 17).”
BackgroundMethodNelson, F., Zvirbulis, R., Zonca, B., Li, K.-W., Turner, S., Pasierb, M., Wilton, P., Martínez-Puig, D., & Wu, W. (2014) · Rheumatology International · doi:10.1007/s00296-014-3047-6 · Cited by 55
“Patients with OA have elevated levels of inflammatory cytokines and chemokines in their SF [37].”
BackgroundWang, H., Yan, Y., Pathak, J. L., Hong, W., Zeng, J., Qian, D., Hao, B., Li, H., Gu, J., Jaspers, R. T., et al. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17672 · Cited by 63
Li, X., Xu, Q., Johnson, M., Wang, X., Lyu, J., Li, Y., Mcmahon, S., Greiser, U., A, S., & Wang, W.-X. (2021) · Biomaterials Science · doi:10.1039/d1bm00482d · Cited by 54
Wang, Y.-Y., Zeng, S.-W., Crunteanu, A., Xie, Z., Humbert, G., Ma, L.-B., Wei, Y.-Y., Brunel, A., Bessette, B., Orlianges, J., et al. (2020) · Nano-Micro Letters · doi:10.1007/s40820-021-00613-7 · Cited by 54
Ding, S., Pang, Z., Chen, X., Li, Z., Liu, X., Zhai, Q., Huang, J., & Ruan, Z. (2020) · Journal of Inflammation · doi:10.1186/s12950-020-00242-8 · Cited by 63
Feng, Z.-H., Zheng, W., Li, X., Lin, J., Xie, C., Li, H., Cheng, L., Wu, A., & Ni, W. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.06.017 · Cited by 54
“F, we found that IL-1β markedly increased the expression of iNOs, COX-2, MMP-3, MMP-13, and ADAMTS-5 compared to the control group.”
BackgroundInfluentialRaines, A., Shih, M., Chua, L., Su, C.-W., Tseng, S. C. G., & O’Connell, J. (2016) · Tissue Engineering. Part A · doi:10.1089/ten.tea.2016.0088 · Cited by 54
“7 43 These studies highlight the importance of inflammation as a contributor to OA, and current therapies for OA primarily target relieving pain associated with OA by reducing in-flammation, as is the case with NSAIDs, corticosteroid injections, and HA injections.”
Mechanotransduction pathways in bone pathobiology
Spyropoulou, A., Karamesinis, K., & Basdra, E. K. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.05.010 · Cited by 55
“cartilage which also largely affects synovial membrane and subchondral bone [10].”
BackgroundLi, W., Du, C.-X., Wang, H., & Zhang, C. (2014) · Genetics and Molecular Research · doi:10.4238/2014.november.14.9 · Cited by 54
“However, the etiology and pathogenesis underlying this disease are poorly understood (Kapoor et al., 2011).”
BackgroundDeng, Z., Yang, C. H., Xiang, T., Dou, C., Sun, D., Dai, Q., Ling, Z., Xu, J., Luo, F., & Chen, Y. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02447-y · Cited by 55
Joint together: The etiology and pathogenesis of ankylosing spondylitis
Xiong, Y., Cai, M., Xu, Y., Dong, P., Chen, H., He, W., & Zhang, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.996103 · Cited by 65
Tang, S., Nie, X., Ruan, J., Cao, Y., Kang, J., & Ding, C. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05148-2 · Cited by 56
“RESULTS circNFKB1 is upregulated in inflamed chondrocytes and osteoarthritic cartilage Accumulating evidences demonstrate that NF-κB signaling pathway plays an essential role in the pathogenesis of OA [34].”
BackgroundZhu, J., Zhu, Y., Xiao, W., Hu, Y., & Li, Y. (2020) · Annals of Translational Medicine · doi:10.21037/atm.2020.02.103 · Cited by 61
“These proinflammatory factors are strong driving forces of cartilage matrix degeneration and periarticular inflammation (19).”
BackgroundNanus, D., Wijesinghe, S. N., Pearson, M., Hadjicharalambous, M. R., Rosser, A., Davis, E. T., Lindsay, M., & Jones, S. W. (2020) · Arthritis & Rheumatology · doi:10.1002/art.41158 · Cited by 53
Piao, S., Du, W., Wei, Y., Yang, Y., Feng, X., & Bai, L. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.106043 · Cited by 53
Accelerating functional gene discovery in osteoarthritis
Butterfield, N. C., Curry, K. F., Steinberg, J., Dewhurst, H. F., Komla-Ebri, D. S. K., Mannan, N. S., Adoum, A., Leitch, V. D., Logan, J. G., Waung, J. A., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20761-5 · Cited by 63
Characterization of synovial fluid cytokine profiles in chronic meniscal tear of the knee
Bigoni, M., Turati, M., Sacerdote, P., Gaddi, D., Piatti, M., Castelnuovo, A., Franchi, S., Gandolla, M., Pedrocchi, A., Omeljaniuk, R. J., et al. (2017) · Journal of Orthopaedic Research · doi:10.1002/jor.23272 · Cited by 53
“IL-1ß and TNFa are generally acknowledged as primary inflammatory mediators associated with cartilage degeneration, bone changes, and synovial inflammation.(21) In contrast to the abundance of data obtained in patients with ACL rupture, there are few available regarding cytokine levels in chronic isolated meniscal tea…”
BackgroundSystemic inflammation and painful joint burden in osteoarthritis: a matter of sex?
Perruccio, A., Chandran, V., Power, J., Kapoor, M., Mahomed, N., & Gandhi, R. (2015) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2016.08.001 · Cited by 53
Self-citationAsymmetrical lower extremity loading after ACL reconstruction: more than meets the eye.
Chmielewski, T. (2011) · Journal of Orthopaedic and Sports Physical Therapy · doi:10.2519/jospt.2011.0104 · Cited by 53
Smith, J. K. (2020) · Life · doi:10.3390/life10090207 · Cited by 52
Cellular senescence and other age-related mechanisms in skeletal diseases
Li, K., Hu, S., & Chen, H. (2025) · Bone Research · doi:10.1038/s41413-025-00448-7 · Cited by 58
“103 Research has con fi rmed that the number of senescent chondrocytes is directly proportional to the severity of OA.”
Li, H., Zhao, T., Yuan, Z., Gao, T., Yang, Y., Li, R., Tian, Q., Tang, P., Guo, Q., & Zhang, L. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.06.037 · Cited by 33
“Traumatic or chronic damage to the articular cartilage modifies the load-bearing capacity of the joint, leading to abnormal joint loading, fibroblast activation, macrophage activation, and the production of proinflammatory agents, exacerbating cartilage injury [54].”
BackgroundEpelboym, Y., Mandell, J., Collins, J., Burch, E., Shiang, T., Killoran, T., MacFarlane, L., & Guermazi, A. (2023) · Cardiovascular and Interventional Radiology · doi:10.1007/s00270-023-03422-0 · Cited by 52
“Osteoarthritis is a complex disease in which inflammatory mediators are released by cartilage, bone, and synovium [6, 7].”
BackgroundMatejová, J., Špaková, T., Harvanová, D., Lacko, M., Filip, V., Šepitka, R., Mitró, I., & Rosocha, J. (2020) · Cartilage · doi:10.1177/1947603520946385 · Cited by 52
Treatment of Knee Meniscus Pathology: Rehabilitation, Surgery, and Orthobiologics
Chirichella, P., Jow, S., Iacono, S. A., Wey, H. E., & Malanga, G. (2019) · PM & R : the journal of injury, function, and rehabilitation · doi:10.1016/j.pmrj.2018.08.384 · Cited by 52
“generally acknowledged as primary inflammatory mediators associated with cartilage degeneration, bone changes, and synovial inflammation in the setting of osteoarthritis [63] and their presence has suppressed meniscal repair in vitro [64].”
BackgroundCulvenor, A., Eckstein, F., Wirth, W., Lohmander, L., & Frobell, R. (2019) · British Journal of Sports Medicine · doi:10.1136/bjsports-2018-100167 · Cited by 52
Urate and Osteoarthritis: Evidence For a Reciprocal Relationship
Neogi, T., Krasnokutsky, S., & Pillinger, M. (2018) · Joint, bone, spine : revue du rhumatisme · doi:10.1016/j.jbspin.2018.11.002 · Cited by 52
“Additionally, OA has been associated with IL-1β response genes [14], of potential relevance to gout since IL-1β is a central mediator of the gouty inflammatory response [15].”
BackgroundThemistocleous, G., Chloros, G., Kyrantzoulis, I. M., Georgokostas, I., Themistocleous, M., Papagelopoulos, P., & Savvidou, O. (2018) · Heliyon · doi:10.1016/j.heliyon.2018.e00871 · Cited by 52
“Although OA is a process of articular cartilage “wear and tear”, its changes are biochemically mediated [10], through an imbalance between intra-articular anabolic and catabolic cytokines [11].”
BackgroundLiu, Y., Zhu, H., Yan, X., Gu, H.-Y., Gu, Z., & Liu, F. (2017) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2017.07.094 · Cited by 52
Alshenibr, W., Tashkandi, M. M., Alsaqer, S. F., Alkheriji, Y., Wise, A., Fulzele, S., Mehra, P., Goldring, M., Gerstenfeld, L., & Bais, M. (2017) · Arthritis Research & Therapy · doi:10.1186/s13075-017-1388-8 · Cited by 52
“Anti-cytokine agents have been evaluated for OA therapy, but with limited success [9, 10].”
BackgroundThe IL-1 family in fish: Swimming through the muddy waters of inflammasome evolution
Ogryzko, N. V., Renshaw, S. A., & Wilson, H. L. (2014) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2014.03.008 · Cited by 47
Henrotin, Y., Lambert, C., & Richette, P. (2014) · Seminars in Arthritis & Rheumatism · doi:10.1016/j.semarthrit.2013.10.005 · Cited by 52
Advances and challenges in gene‐based approaches for osteoarthritis
Madry, H., & Cucchiarini, M. (2013) · The Journal of Gene Medicine · doi:10.1002/jgm.2741 · Cited by 52
Venkatesan, J., Rey-Rico, A., Schmitt, G., Wezel, A., Madry, H., & Cucchiarini, M. (2013) · Journal of Translational Medicine · doi:10.1186/1479-5876-11-211 · Cited by 52
“; licensee BioMed Cen Creative Commons Attribution License (http:/ distribution, and reproduction in any medium irreversible degradation of the articular cartilage in OA, associated with a remodeling of the subchondral bone and osteophyte formation, is the result of an impaired cartilage homeostasis (prevalence of cat…”
BackgroundWeng, L.-H., Ko, J.-Y., Wang, C.-J., Sun, Y.-C., & Wang, F.-S. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34602 · Cited by 52
Peptide-based delivery to bone
Aoki, K., Alles, N., Soysa, N. S., & Ohya, K. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.05.017 · Cited by 59
Breaking Down Osteoarthritis: Exploring Inflammatory and Mechanical Signaling Pathways
Batarfi, W. A., Yunus, M. H. M., Hamid, A. A., Maarof, M., & Rani, R. A. (2025) · Life · doi:10.3390/life15081238 · Cited by 46
“Additionally, the OA chondrocytes express a wide range of NF-kB-mediated catabolic cytokines and chemokines, such as TNF-α , IL-1 β , IL-6, and IL-8, which boost NF-kB activation by increasing MMPs production, reducing collagen and proteoglycan synthesis, and acting in a positive feedback loop [49].”
Bile acid metabolism regulatory network orchestrates bone homeostasis
Xiang, T., Deng, Z., Yang, C. H., Tan, J., Dou, C., Luo, F., & Chen, Y. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106943 · Cited by 54
Latest insights in disease-modifying osteoarthritis drugs development
Li, S., Cao, P., Chen, T., & Ding, C. (2023) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x231169839 · Cited by 53
Rare earth-based materials for bone regeneration: Breakthroughs and advantages
Huang, Y., Zhai, X., Ma, T., Zhang, M., Pan, H., Lu, W. W., Zhao, X., Sun, T., Li, Y., Shen, J., et al. (2021) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2021.214236 · Cited by 60
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Critical role for arginase II in osteoarthritis pathogenesis
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Interplay of Inflammatory Mediators with Epigenetics and Cartilage Modifications in Osteoarthritis
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“It is becoming increasingly evident that multiple inflammatory mediators were released into the synovial fluid of joint that serve an important role in initiation and progression of synovial inflammation and articular cartilage degradation (Kapoor et al., 2011).”
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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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