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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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Anti-inflammatory and anti-osteoarthritis effect of Mollugo pentaphylla extract
Lee, Y.-M., Son, E., Kim, S.-H., Kim, O., & Kim, D.-S. (2019) · Pharmaceutical Biology · doi:10.1080/13880209.2018.1557700 · Cited by 50
“The primary goals of current arthritis therapy are pain control, a reduction in inflammation, and improved joint function (Kapoor et al. 2011; Sokolove and Lepus 2013).”
BackgroundTamura, T., Higuchi, Y., Kitamura, H., Murao, N., Saitoh, R., Morikawa, T., & Sato, H. (2016) · Arthritis Research & Therapy · doi:10.1186/s13075-016-0971-8 · Cited by 50
“These findings may indicate that there is a common underlying mechanism contributing to synovial inflammation in RA and OA, and that MTX might be a therapeutic option in the treatment of certain types of OA [3, 13, 14].”
BackgroundLacy, S. E., Wu, C., Ambrosi, D. J., Hsieh, C.-M., Bose, S., Miller, R., Conlon, D., Tarcsa, E., Chari, R. V. J., Ghayur, T., et al. (2015) · mAbs · doi:10.1080/19420862.2015.1026501 · Cited by 58
“Preclinical and clinical studies provide significant evidence for the role of IL-1 in the pathogenesis of OA, including cartilage degradation, bone sclerosis, and synovial proliferation.(20) IL-1a and IL-1b are expressed in the cartilage and synovial membrane and fluid of patients with OA.”
BackgroundJiao, K., Zhang, J., Zhang, M., Wei, Y.-Y., Wu, Y., Qiu, Z.-Y., He, J.-J., Cao, Y.-X., Hu, J.-T., Zhu, H., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053312 · Cited by 50
“Exogenous TNF-a increased CD163 expression in primary chondrocytes and promoted migration and phagocytosis TNF-a is believed to be a critical mediator in the disturbed metabolism and enhanced catabolism of degraded joint cartilage, even in the early stages of cartilage degradation [25].”
BackgroundCytokines: The links between bone and the immune system
Cai, L., Lv, Y., Yan, Q., & Guo, W. (2023) · Injury · doi:10.1016/j.injury.2023.111203 · Cited by 50
Wang, D., Chai, X.-Q., Hu, S.-S., & Pan, F. (2021) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2021.11.014 · Cited by 65
Gomoll, A., Farr, J., Cole, B., Flanigan, D., Lattermann, C., Mandelbaum, B., Strickland, S. M., Zaslav, K., Kimmerling, K., & Mowry, K. (2021) · Arthroscopy: The Journal of Arthroscopy And Related · doi:10.1016/j.arthro.2021.02.044 · Cited by 49
Xue, H., Tu, Y.-H., Ma, T., Wen, T., Yang, T., Xue, L., Cai, M.-W., Wang, F.-X., & Guan, M.-Y. (2019) · Bone · doi:10.1016/j.bone.2019.03.035 · Cited by 49
Tang, H.-Q., He, S.-B., Zhang, X.-Y., Luo, S.-L., Zhang, B.-X., Duan, X.-J., Zhang, Z.-Q., Wang, W.-Q., Wang, Y., & Sun, Y.-K. (2016) · Evidence-Based Complementary and Alternative Medicine · doi:10.1155/2016/3246946 · Cited by 49
“According to reports, high levels of IL-1β can be found in the synovial membrane, synovial fluid, cartilage tissue, and subchondral bone tissue of OA patients [39].”
Zhao, Y.-P., Li, Z., Wang, W.-H., Zhang, H., Chen, J.-Y., Su, P., Liu, L., & Li, W.-W. (2015) · Inflammation · doi:10.1007/s10753-015-0260-8 · Cited by 49
Gómez-Gaete, C., Retamal, M., Chávez, C., Bustos, P., Godoy, R., & Torres‐Vergara, P. (2016) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2016.10.010 · Cited by 57
“After LPS stimulation and further treatmentwithMPs, the cell-free supernatantswere collected and used for measurement of cytokine concentrations with ELISA kits for IL-1 and TNF-α, according to the manufacturer's instructions (Ready-SET-Go!”
BackgroundInfluentialMartel‐Pelletier, J., Barr, A., Cicuttini, F., Conaghan, P. G., Cooper, C. C., Goldring, M. B., Goldring, S. R., Jones, G., Teichtahl, A. J., & Pelletier, J. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.72 · Cited by 2,040
Self-citationExploring the Role of Hormones and Cytokines in Osteoporosis Development
Umur, E., Bulut, S. B., Yiğit, P., Bayrak, E., Arkan, Y., Arslan, F., Baysoy, E., Kaleli‐Can, G., & Ayan, B. (2024) · Biomedicines · doi:10.3390/biomedicines12081830 · Cited by 42
“These molecules are effective in initiating and sustaining inflammation, thereby enabling the immune system to effectively combat pathogens [121,122].”
BackgroundChen, Q.-Z., Jin, Y.-X., Chen, T., Zhou, H., Wang, X., Wu, O.-Q., Chen, L.-J., Zhang, Z., Guo, Z., Sun, J., et al. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.100993 · Cited by 48
Gan, H., Ramlee, M. H., Wahab, A. A., Lee, Y. S., & Shimizu, A. (2020) · Artificial Intelligence Review · doi:10.1007/s10462-020-09924-4 · Cited by 53
Hanafy, A., & El-Ganainy, S. O. (2019) · International journal of pharmaceutics · doi:10.1016/j.ijpharm.2019.118859 · Cited by 48
Jones, I. A., Wilson, M. L., Togashi, R., Han, B., Mircheff, A. K., & Vangsness, C. T. (2018) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-018-2300-7 · Cited by 56
Levings, R. W., Broome, T. A., Smith, A. D., 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.2017.142 · Cited by 64
“Among the more promising candidates is interleukin-1 receptor antagonist (IL-1Ra), which functions as a competitive inhibitor of interleukin-1 (IL-1),(3) a primary inflammatory cytokine and mediator of cartilage degradation.(4,5) Unfortunately, the administration of the recombinant forms of proteins, such as IL-1Ra (A…”
BackgroundHu, X., Ji, X., Yang, M., Fan, S., Wang, J.-R., Lu, M., Shi, W., Mei, L., Xu, C.-Y., Fan, X., et al. (2018) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3380 · Cited by 48
“Thus, intra-articular inhibition of Cdc42 activity potently attenuated articular cartilage degeneration in mice with experimental OA.”
ResultInfluentialHydrogen Sulfide and Inflammatory Joint Diseases.
Burguera, E. F., Meijide-Faílde, R., & Blanco, F. (2017) · Current Drug Targets · doi:10.2174/1389450117666160829112824 · Cited by 48
“Particularly in OA, IL-1β is a key pro-inflammatory factor (Reviewed in [6-8]).”
Backgroundda Cunha, A. L., de Aguiar, J. A. K., da Silva, F. S. C., & Michelacci, Y. M. C. D. S. (2017) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2017.05.123 · Cited by 47
ATF3 deficiency in chondrocytes alleviates osteoarthritis development
Iezaki, T., Ozaki, K., Fukasawa, K., Inoue, M., Kitajima, S., Muneta, T., Takeda, S., Fujita, H., Onishi, Y., Horie, T., et al. (2016) · The Journal of Pathology · doi:10.1002/path.4739 · Cited by 52
“Pro-inflammatory cytokines are believed to be responsible for the disruption of cartilage homeostasis and initiation of the catabolic pathway in addition to mechanical stress [28,29].”
BackgroundPresence of Gout is Associated With Increased Prevalence and Severity of Knee Osteoarthritis
Howard, R. G., Samuels, J., Gyftopoulos, S., Krasnokutsky, S., Leung, J., Swearingen, C., & Pillinger, M. (2015) · Journal of clinical rheumatology · doi:10.1097/rhu.0000000000000217 · Cited by 48
“Whereas OA is initiated by mechanical stress on cartilage, its progression depends on cellular and biochemical factors, including chondrocyte activation and the secretion of inflammatory mediators.(3) Molecules implicated in OA pathogenesis include cytokines such as interleukin 1β (IL-1β), which stimulates metalloprot…”
BackgroundHeard, B., Rosvold, J., Fritzler, M., El-Gabalawy, H., Wiley, J., & Krawetz, R. (2014) · Journal of the Royal Society Interface · doi:10.1098/rsif.2014.0428 · Cited by 48
Xu, J.-K., Pei, Y., Lu, J., Liang, X.-J., Li, Y., Wang, J.-H., & Zhang, Y.-G. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.107150 · Cited by 47
Semaphorin 3A Inhibits Inflammation in Chondrocytes under Excessive Mechanical Stress
Sumi, C., Hirose, N., Yanoshita, M., Takano, M., Nishiyama, S., Okamoto, Y., Asakawa, Y., & Tanimoto, K. (2018) · Mediators of Inflammation · doi:10.1155/2018/5703651 · Cited by 47
Kerschenmeyer, A., Arlov, Ø., Malheiro, V., Steinwachs, M., Rottmar, M., Maniura-Weber, K., Palazzolo, G., & Zenobi-Wong, M. (2017) · Biomaterials Science · doi:10.1039/c7bm00341b · Cited by 47
An overview of the role of lipid peroxidation-derived 4-hydroxynonenal in osteoarthritis
Abusarah, J., Bentz, M., Benabdoune, H., Rondon, P., Shi, Q., Fernandes, J., Fahmi, H., & Benderdour, M. (2017) · Inflammation Research · doi:10.1007/s00011-017-1044-4 · Cited by 47
“Degradation of cartilage ECM and the suppression of its biosynthesis by chondrocyte are also regulated by the release of pro-inflammatory cytokines in the joint [9].”
BackgroundSelf-citationRasheed, N., Alghasham, A. A., & Rasheed, Z. (2016) · Pharmacognosy Research · doi:10.4103/0974-8490.175612 · Cited by 47
“[38] Now it is widely accepted that the onset of OA is well associated with excessive production of pro‑inflammatory cytokines including IL‑1β.[9,39] It is well documented that IL‑1β has a pivotal role in cartilage matrix destruction via upregulation of the production of proteases and downregulation of the synthesis o…”
BackgroundFernandes, M. T. P., Fernandes, K. B. P., Marquez, A. S., Cólus, I. M. S., de Souza, M. F., Santos, J. P. M., & Poli‐Frederico, R. C. (2015) · Cytokine · doi:10.1016/j.cyto.2015.07.020 · Cited by 42
Dong, T., Chang, H., Zhang, F., Chen, W., Zhu, Y.-B., Wu, T., & Zhang, Y.-Z. (2015) · International Orthopaedics · doi:10.1007/s00264-015-2744-4 · Cited by 47
“pathogenesis by increasing the cartilage degradation and sensitivity to pain via a number of direct and indirect actions [5, 9, 10].”
BackgroundWu, Y., Shen, S., Chen, J.-X., Ni, W., Wang, Q., Zhou, H., Chen, J.-X., Zhang, H., Mei, Z.-X., Sun, X.-W., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade5584 · Cited by 46
“…factors, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor – α (TNF-α), and subsequently result in the activation of matrix metalloproteinases (MMPs) and A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), eventually leading to ECM degeneration ( 2 ).”
Qin, H.-C., Du, L., Luo, Z., He, Z.-Q., Wang, Q., Chen, S.-Y., & Zhu, Y.-L. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1080430 · Cited by 46
“IL-1β also plays a significant role in the pathogenesis of OA and is substantially expressed in OA patients (Kapoor et al., 2011).”
BackgroundLi, H., Zhang, X., Gu, L.-L., Li, Q., Ju, Y., Zhou, X., Hu, M.-H., & Li, Q. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.801910 · Cited by 46
“Some effective gout therapy treatments based on the pathogenesis of gout include inflammation reduction, pain relief, and improved joint function achieved by reducing the levels of UA in serum/urine and dissolving MSU crystals (Martinon 2010; Kapoor et al., 2011; Sokolove and Lepus 2013; Hainer et al., 2014).”
BackgroundLi, S.-S., Wang, H., Zhang, Y., Qiao, R., Xia, P., Kong, Z., Zhao, H.-B., & Yin, L. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.721258 · Cited by 46
Non-surgical osteoarthritis therapy, intra-articular drug delivery towards clinical applications
Liang, Y.-J., Xu, X., Xu, L., Prasadam, I., Duan, L., Xiao, Y., & Xia, J. (2020) · Journal of drug targeting (Print) · doi:10.1080/1061186x.2020.1870231 · Cited by 46
“These factors, in turn, enhance the generation of cartilage matrix-degrading enzymes, which eventually exacerbate cartilage catabolism and lead to progressive OA [5].”
BackgroundComplement Expression and Activation in Osteoarthritis Joint Compartments
Assirelli, E., Pulsatelli, L., Dolzani, P., Mariani, E., Lisignoli, G., Addimanda, O., & Meliconi, R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.535010 · Cited by 46
“Indeed, a recent study showed the non-involvement of IL-1b in synovial inflammation and cartilage destruction during collagenase-induced OA and it was suggested that other inflammatory mediators (possibly the alarmins, IL-6 and IL-17) could be responsible for the joint damage (43, 44).”
BackgroundChen, W.-S., Chen, L.-W., Zhang, Z.-J., Meng, F., Huang, G., Sheng, P., Zhang, Z.-Q., & Liao, W. (2016) · Biochimica et Biophysica Acta · doi:10.1016/j.bbamcr.2016.09.010 · Cited by 46
Zhou, X.-D., Lin, X., Xiong, Y., Jiang, L.-F., Li, W.-J., Li, J., & Wu, L.-D. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.02.029 · Cited by 46
“The current OA paradigm includes an active biological process of matrix degradation leading to the release of MMPs and eventually cartilage loss and both acute and chronic inflammatory processes mediate disease progression [28].”
BackgroundPascarelli, N., Collodel, G., Moretti, E., Cheleschi, S., & Fioravanti, A. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161125936 · Cited by 46
Inflammatory cytokine response following acute tibial plateau fracture.
Haller, J., McFadden, M., Kubiak, E. N., & Higgins, T. (2015) · Journal of Bone and Joint Surgery. American volume · doi:10.2106/jbjs.n.00200 · Cited by 46
Michelacci, Y. M., Baccarin, R., & Rodrigues, N. N. P. (2023) · Life · doi:10.3390/life13071460 · Cited by 45
von Kaeppler, E. P., Wang, Q., Raghu, H., Bloom, M. S., Wong, H., & Robinson, W. (2021) · Clinical Immunology · doi:10.1016/j.clim.2021.108784 · Cited by 45
“Of note, increased Tnfa expression is associated with both proinflammatory M1 macrophage phenotype [40,44] and OA [45], underscoring the understanding of the OA joint as a proinflammatory environment.”
BackgroundMustonen, A.-M., & Nieminen, P. (2021) · Pharmaceuticals · doi:10.3390/ph14040315 · Cited by 45
“These results have clear translational potential, as IL-1β is also one of the main mediators of cartilage destruction in OA patients [51].”
BackgroundImmunoengineering the Next Generation of Arthritis Therapies
Klimak, M., Nims, R. J., Pferdehirt, L., Collins, K. H., Harasymowicz, N. S., Oswald, S. J., Setton, L. A., & Guilak, F. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.03.062 · Cited by 48
“and IL-8 as well as CCL2 and other various chemokines [30].”
Lactobacillus acidophilus ameliorates pain and cartilage degradation in experimental osteoarthritis.
Lee, S.-H., Kwon, J., Jhun, J., Jung, K., Park, S.-H., Yang, C.-W., Cho, Y., Kim, S.-J., & Cho, M. (2018) · Immunology Letters · doi:10.1016/j.imlet.2018.07.003 · Cited by 45
Zhao, L., Wang, L., Di, S.-N., Xu, Q., Ren, Q.-C., Chen, S.-Z., Huang, N., Jia, D., & Shen, X. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.06.019 · Cited by 56
Adams, S. B., Nettles, D. L., Jones, L. C., Miller, S. D., Guyton, G. P., & Schon, L. C. (2014) · Foot & Ankle International · doi:10.1177/1071100714550652 · Cited by 46
“The presence of proinflammatory and anti-inflammatory cytokines in OA and rheumatoid arthritis is widely documented.(14,22,34,35) However, the role of inflammatory cytokines in posttraumatic arthritis is not well understood.”
BackgroundInterleukin 6 Mediates Select Effects of Notch in Chondrocytes
Zanotti, S., & Canalis, E. (2013) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2013.08.010 · Cited by 45
Isola, M., Ferrari, V., Miolo, A., Stabile, F., Bernardini, D., Carnier, P., & Busetto, R. (2011) · Veterinary and comparative orthopaedics and traumatology · doi:10.3415/vcot-10-04-0051 · Cited by 45
“Indeed, both in humans and dogs the hypothesis that NGF might somehow be involved in the pathogenic cascade of OA joint inflammation and pain has been supported by several findings such as the NGF receptor expression upregulation in the synovial compartment, the increased local release of NGF according to the degree o…”
BackgroundZhang, Z., Xie, S., Qian, J., Gao, F., Jin, W., Wang, L., Yan, L., Chen, H., Yao, W., Li, M., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04313-1 · Cited by 53
“Of note, the number of macrophages and inflammatory factor expression increased in the synovium of OA[30].”
Background“Cross-talk” between gut microbiome dysbiosis and osteoarthritis progression: a systematic review
Liu, S., Li, G., Xu, H., Wang, Q., Wei, Y., Yang, Q., Xiong, A., Yu, F., Weng, J., & Zeng, H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1150572 · Cited by 40
“Frontiers in Immunology 12 secondary inflammation of the joints (82, 83).”
BackgroundThe potential role and trend of HIF‑1α in intervertebral disc degeneration: Friend or foe? (Review)
Li, Y., Liu, S., Pan, D., Xu, B., Xing, X., Zhou, H., Zhang, B., Zhou, S., Ning, G., & Feng, S. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.11878 · Cited by 45
Otahal, A., Kramer, K., Kuten-Pella, O., Weiss, R., Stotter, C., Lacza, Z., Weber, V., Nehrer, S., & Luna, A. D. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.584050 · Cited by 63
NOV/CCN3 induces cartilage protection by inhibiting PI3K/AKT/mTOR pathway
Huang, X., Ni, B., Mao, Z., Yang, X., Chu, X., Zhang, R., Ma, X., & You, H. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14621 · Cited by 48
Osman, W. N. W., Tantowi, N. A. C. A., Lau, S. F., & Mohamed, S. (2019) · Journal of food biochemistry · doi:10.1111/jfbc.12755 · Cited by 44
Wang, Y., Teichtahl, A. J., Pelletier, J., Abram, F., Wluka, A. E., Hussain, S. M., Martel‐Pelletier, J., & Cicuttini, F. (2018) · Rheumatology · doi:10.1093/rheumatology/key274 · Cited by 48
Self-citationPhospholipid-Coated Mesoporous Silica Nanoparticles Acting as Lubricating Drug Nanocarriers
Sun, T., Sun, Y., & Zhang, H.-Y. (2018) · Polymers · doi:10.3390/polym10050513 · Cited by 44
“In terms of treating early stage OA, selected drugs are employed in order to reduce inflammation, such as bisphosphonates [5] and receptor antagonists [6].”
BackgroundRey-Rico, A., Frisch, J., Venkatesan, J. K., Schmitt, G., Rial-Hermida, I., Taboada, P., Concheiro, A., Madry, H., Alvarez-Lorenzo, C., & Cucchiarini, M. (2016) · ACS Applied Materials and Interfaces · doi:10.1021/acsami.6b06509 · Cited by 44
Immunomodulatory properties of stem cells and bioactive molecules for tissue engineering
Molina, E. R., Smith, B. T., Shah, S. R., Shin, H., & Mikos, A. G. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.038 · Cited by 44
“Delivery of Pro-inflammatory Cytokines As previously discussed, pro-inflammatory cytokines have been shown to be intricately linked with the pathophysiology of several disease states such as osteoarthritis and MS [107,108].”
BackgroundProteomic profiling and functional characterization of early and late shoulder osteoarthritis
Wanner, J. P., Subbaiah, R., Skomorovska-Prokvolit, Y., Shishani, Y. F., Boilard, É., Mohan, S., Gillespie, R., Miyagi, M., & Gobezie, R. (2013) · Arthritis Research & Therapy · doi:10.1186/ar4369 · Cited by 44
“Several proinflammatory cytokines have been implicated as possible therapeutic targets with existing research indicating that IL-1β, IL-6 and TNF-α are the major proinflammatory cytokines in OA [6].”
BackgroundMobasheri, A., & Shakibaei, M. (2013) · Histology and Histopathology · doi:10.14670/hh-28.955 · Cited by 44
“This makes IL-1ß and its cell surface receptor as well as downstream inflammatory signaling pathways prime targets for therapeutic strategies (Kapoor et al., 2011).”
BackgroundCampo, G. M., Avenoso, A., D’Ascola, A., Scuruchi, M., Prestipino, V., Nastasi, G., Calatroni, A., & Campo, S. (2012) · FEBS Journal · doi:10.1111/j.1742-4658.2012.08598.x · Cited by 43
Li, C., Li, W., Pu, G., Wu, J., & Qin, F. (2022) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-022-03437-2 · Cited by 45
Sanjeewa, K. K. A., Nagahawatta, D. P., Yang, H.-W., Oh, J. Y., Jayawardena, T. U., Jeon, Y., Zoysa, M. D., Whang, I., & Ryu, B. (2020) · Biomolecules · doi:10.3390/biom10040511 · Cited by 44
UFL1 attenuates IL-1β-induced inflammatory response in human osteoarthritis chondrocytes.
Yang, G., Wang, Y., Chen, Y., & Huang, R. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106278 · Cited by 43
Huang, W. H., Cheng, C., Shan, W., Ding, Z., Liu, F., Lu, W. D., He, W., Xu, J., & Yin, Z. (2019) · FEBS Journal · doi:10.1111/febs.15009 · Cited by 43
Potential Novel Prediction of TMJ-OA: MiR-140-5p Regulates Inflammation Through Smad/TGF-β Signaling
Li, W.-H., Zhao, S., Yang, H.-F., Zhang, C., Kang, Q., Deng, J., Xu, Y.-H., Ding, Y., & Li, S. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00015 · Cited by 43
“Interleukins-1β is believed to be critical in cartilage damage because it can restrain matrix protein synthesis and induces proinflammatory cytokines (Kapoor et al., 2011).”
BackgroundThe Metabolome and Osteoarthritis: Possible Contributions to Symptoms and Pathology
Rockel, J., & Kapoor, M. (2018) · Metabolites · doi:10.3390/metabo8040092 · Cited by 43
“For instance, BCAAs increase migration of mononuclear cells via activation of mTORC1 [133], suggesting the potential for increased inflammation, an underlying pathology of OA [134].”
BackgroundSelf-citationO’Brien, K., Tailor, P., Leonard, C., Difrancesco, L., Hart, D., Matyas, J., Frank, C., & Krawetz, R. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040774 · Cited by 43
“Of significant importance in OA pathology is the interaction of articular cartilage and synovium [9,13,14].”
Mével, E., Merceron, C., Vinatier, C. S., Krisa, S., Richard, T., Masson, M., Lesoeur, J., Hivernaud, V., Gauthier, O., Abadie, J., et al. (2016) · Scientific Reports · doi:10.1038/srep33527 · Cited by 49
“IL-1 β is one of the pivotal cytokines involved in both degradative and inflammatory pathway associated to OA progression 47,48 .”
Abella, V., Scotece, M., Conde, J., López, V., Pirozzi, C., Pino, J., Gómez, R., Lago, F., González-Gay, M. Á., & Gualillo, O. (2016) · Scientific Reports · doi:10.1038/srep20356 · Cited by 45
Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis
Huh, Y., Lee, G., Song, W.-H., Koh, J., & Ryu, J.-H. (2015) · Experimental and Molecular Medicine · doi:10.1038/emm.2015.88 · Cited by 43
Possible role of methylglyoxal and glyoxalase in arthritis.
Ahmed, U., Thornalley, P. J., & Rabbani, N. (2014) · Biochemical Society Transactions · doi:10.1042/bst20140024 · Cited by 43
Yu, D., Liu, F.-X., Liu, M., Zhao, X., Wang, X.-Q., Li, Y., Mao, Y.-Q., & Zhu, Z. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077824 · Cited by 43
“Synovial reaction in OA, which involves synovial hyperplasia, subsynovial tissue proliferation and inflammatory cell infiltration, is a primary source of the inflammatory mediators that produce pain [5,40].”
BackgroundCorrelation of synovial fluid HMGB-1 levels with radiographic severity of knee osteoarthritis.
Li, Z., Cheng, G.-Q., Hu, K.-Z., Li, M.-Q., Zang, W.-P., Dong, Y.-Q., Wang, W.-L., & Liu, Z.-D. (2011) · Clinical and investigative medicine. Medecine clinique et experimentale · doi:10.25011/cim.v34i5.15673 · Cited by 43
“Increasingly, evidence in both experimental and clinical studies suggests that in ammatory molecules such as proin ammatory cytokines are among the critical mediators of the disturbed processes implicated in OA pathophysiology, suggesting that OA is a chronic in ammatory process [3].”
BackgroundBone and Joint‐on‐Chip Platforms: Construction Strategies and Applications
Du, C., Liu, J., Liu, S., Xiao, P., Chen, Z., Chen, H., Huang, W., & Lei, Y. (2024) · Small Methods · doi:10.1002/smtd.202400436 · Cited by 47
Fang, Y., Lou, C., Lv, J., Zhang, C., Zhu, Z., Hu, W. M., Chen, H., Sun, L., & Zheng, W. (2024) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2024.04.004 · Cited by 37
“Numerous investigations have confirmed a strong association be-tween inflammatory cytokines and the onset and advancement of OA [5].”
BackgroundComparison of the effects of oxidative and inflammatory stresses on rat chondrocyte senescence
Yagi, M., Endo, K., Komori, K., & Sekiya, I. (2023) · Scientific Reports · doi:10.1038/s41598-023-34825-1 · Cited by 45
Xv, Z., He, G., Wang, X.-L., Hao, S., Chen, Y.-J., & Lin, S.-M. (2021) · Animal Feed Science and Technology · doi:10.1016/j.anifeedsci.2021.115012 · Cited by 42
Biomaterial strategies for improved intra‐articular drug delivery
Castro, L. M. M., Garcı́a, A. J., & Guldberg, R. E. (2020) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37074 · Cited by 52
“Furthermore, the synovial membrane is affected by the infiltration of T lymphocytes, neutrophils and macrophages(22), which secrete pro-inflammatory mediators, cytokines and chemokines such as IL-1, IL-6, IL-15, TNF-α, nitric oxide and prostaglandins, which further exacerbate joint inflammation and cartilage degenerat…”
BackgroundNagy, E. E., Nagy-Finna, C., Popoviciu, H. V., & Kovács, B. (2020) · Clinical Interventions in Aging · doi:10.2147/cia.s242288 · Cited by 57
Serum Inflammatory Markers in Patients With Knee Osteoarthritis
Giordano, R., Petersen, K. K., Andersen, H. H., Simonsen, O. H., & Arendt‐Nielsen, L. (2020) · Clinical Journal of Pain · doi:10.1097/ajp.0000000000000804 · Cited by 52
Rey-Rico, A., Venkatesan, J. K., Schmitt, G., Speicher-Mentges, S., Madry, H., & Cucchiarini, M. (2018) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b00331 · Cited by 42
MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression
Chen, W.-S., Sheng, P., Huang, Z.-Y., Meng, F., Kang, Y., Huang, G., Zhang, Z.-Q., Liao, W., & Zhang, Z.-J. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17091377 · Cited by 42
“For example, miR-29b specifically targets HDAC4 to epigenetically regulate multiple myeloma cell growth and survival [1], miR-22 targets and inhibits HDAC4 in antigen-presenting cells and plays a critical role in emphysema and TH17 responses [7], miR-125a-5p targets HDAC4 to suppress breast tumorigenesis [3], and miR-…”
BackgroundLithium Protects Against Cartilage Degradation in Osteoarthritis
Minashima, T., Zhang, Y., Lee, Y.-J., & Kirsch, T. (2014) · Arthritis & Rheumatology · doi:10.1002/art.38373 · Cited by 42
“Proinflammatory cytokines, such as interleukin-1 (IL-1 ), tumor necrosis factor , and IL-6, are critical mediators of the disturbed metabolism and enhanced catabolism of the joints affected by OA (4,5).”
BackgroundXu, M., Zhang, L., Zhao, L., Gao, S.-G., Han, R., Su, D., & Lei, G. (2013) · Rheumatology International · doi:10.1007/s00296-012-2548-4 · Cited by 42
“of cartilage observed in OA, either directly or indirectly by modulating anabolic and catabolic factors [7, 8].”
BackgroundSun, W.-C., Xie, W., Huang, D., Cui, Y., Yue, J.-J., He, Q.-F., Jiang, L.-Y., Xiong, J.-Y., Sun, W., & Yi, Q. (2022) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2022.5190 · Cited by 41
Zhu, W., Tang, H., Cao, L., Zhang, J., Li, J., Ma, D., & Guo, C.-A. (2022) · Chemical Biology and Drug Design · doi:10.1111/cbdd.14056 · Cited by 41
“IL- 1β, a pro- inflammatory cytokine, plays a key role in OA progression (Kapoor et al., 2011).”
BackgroundRegulating Fibrocartilage Stem Cells via TNF-α/Nf-κB in TMJ Osteoarthritis
Bi, R., Chen, K., Wang, Y., Luo, X., Li, Q., Li, P., Yin, Q., Fan, Y., & Zhu, S. (2021) · Journal of dentistry research · doi:10.1177/00220345211037248 · Cited by 41
“TNF-α is a proinflammatory cytokine produced in osteoarthritic joints and is thought to play a critical role in the structural damage that occurs during OA progression (Kapoor et al. 2011).”
BackgroundChen, P., Ruan, A., Zhou, J., Huang, L., Zhang, X., Ma, Y.-F., & Wang, Q.-F. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00949 · Cited by 41
“Although the pathogenesis of KOA remains unclear, inflammation is widely regarded to be an extremely important factor (Kapoor et al., 2011; Berenbaum, 2013; Yang et al., 2016).”
BackgroundDevelopment and Prospect of Intra-Articular Injection in the Treatment of Osteoarthritis: A Review
Zhang, Y., Chen, X.-J., Tong, Y., Luo, J., & Bi, Q. (2020) · Journal of Pain Research · doi:10.2147/jpr.s260878 · Cited by 41
Xia, H.-T., Cao, D.-G., Yang, F., Yang, W.-L., Li, W., Liu, P.-Q., Wang, S., & Yang, F.-Y. (2019) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2019.109708 · Cited by 41
Current concepts in intraosseous Platelet-Rich Plasma injections for knee osteoarthritis.
Delgado, D., Garate, A., Vincent, H., Bilbao, A. M., Patel, R., Fiz, N., Sampson, S., & Sanchez, M. (2019) · Journal of Clinical Orthopaedics and Trauma · doi:10.1016/j.jcot.2018.09.017 · Cited by 41
Glucocorticoid signaling and osteoarthritis.
Savvidou, O., Milonaki, M., Goumenos, S., Flevas, D., Papagelopoulos, P., & Moutsatsou, P. (2019) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2018.11.001 · Cited by 41
Gálvez, I., Torres-Piles, S., & Ortega, E. (2018) · International Journal of Hyperthermia · doi:10.1080/02656736.2018.1502896 · Cited by 41
“In addition to local inflammatory events occurring within joint tissues such as the release of inflammatory mediators by cartilage, bone and synovium [4,5], low-grade systemic inflammation also plays a pivotal role in this condition.”
BackgroundCytokine profiles in osteoporosis suggest a proresorptive bias
Azizieh, F., Raghupathy, R., Shehab, D., Al-jarallah, K., & Gupta, R. (2017) · Menopause · doi:10.1097/gme.0000000000000885 · Cited by 41
Matsui, H., Fukuno, N., Kanda, Y., Kantoh, Y., Chida, T., Nagaura, Y., Suzuki, O., Nishitoh, H., Takeda, K., Ichijo, H., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.536300 · Cited by 41
“Recent studies showed that receptor activator of nuclear factor B ligand (RANKL)3 expression by osteocytes, the majority of bone cells, controls bone remodeling in adults as well as unloading-induced bone loss (9, 10).”
BackgroundInfluentialSun, L., Wang, Y., Kan, T., Wang, H., Cui, J., Wang, L., Liu, C., Li, H., Yu, Z., & Yan, M. (2025) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2025.02.778 · Cited by 48
Lysosomal destabilization: A missing link between pathological calcification and osteoarthritis
Tao, Y., Wang, C., Yan, J., Qin, Z., Qin, W., Ma, Y., Wan, Q., Lu, W., Zhang, M., Tay, F. R., et al. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.12.001 · Cited by 31
“The development of osteoarthritis has been affiliated with inflammation [1 – 4].”
Background
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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