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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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The Biological Basis of Osteoarthritis: State of the Evidence
Malemud, C. (2015) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000162 · Cited by 159
“activated T cells-1 (NFAT1); members of the bone morphogenetic protein family including the BMP, WNT, GREM1, FRZB and DKK1 genes; growth factors, such as transforming growth factor-b, vascular endothelial growth factor and epidermal growth factor [20,21]; leukemia inhibitory factor [22,23];”
BackgroundWang, Y., Xu, J., Zhang, X., Wang, C., Huang, Y., Dai, K., & Zhang, X. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.129 · Cited by 158
“proinflammatory cytokines involved in the pathophysiology of OA.(2) These proinflammatory cytokines upregulate angiogenic factors to stimulate angiogenesis.”
BackgroundInfluentialKloppenburg, M., Ramonda, R., Bobacz, K., Kwok, W.-Y., Elewaut, D., Huizinga, T., Kroon, F., Punzi, L., Smolen, J., Cruyssen, B. V., et al. (2018) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2018-213202 · Cited by 156
Histone deacetylase inhibition activates Nrf2 and protects against osteoarthritis
Cai, D., Yin, S., Yang, J., Jiang, Q., & Cao, W. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0774-3 · Cited by 154
“Proinflammatory cytokines also promote cartilage injuries [36].”
Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling
Zhao, Y., Liu, B., Tian, Q., Wei, J.-L., Richbourgh, B., & Liu, C.-J. (2014) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2014-205779 · Cited by 156
Zhou, F.-F., Zhang, X.-Z., Cai, D., Li, J., Mu, Q., Zhang, W., Zhu, S.-A., Jiang, Y.-Z., Shen, W.-L., Zhang, S.-F., et al. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.09.005 · Cited by 152
Migliorini, F., Driessen, A., Quack, V. M., Sippel, N., Cooper, B., Mansy, Y. E., Tingart, M., & Eschweiler, J. (2020) · Archives of Orthopaedic and Trauma Surgery · doi:10.1007/s00402-020-03551-y · Cited by 163
Larsson, S., Englund, M., Struglics, A., & Lohmander, L. (2015) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2015.05.035 · Cited by 150
Paterson, K., Nicholls, M., Bennell, K., & Bates, D. (2016) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-016-0920-3 · Cited by 145
“Photo-activation of peripheral blood has been previously shown to improve the inflammatory cytokine profile of healthy adults [23] and people with psoriasis [22], and therefore has the potential to improve outcomes in OA where pro-inflammatory cytokines are critical mediators in the pathophysiology of the disease [44].”
BackgroundTargeted and responsive biomaterials in osteoarthritis
Li, J., Zhang, H., Han, Y.-F., Hu, Y., Geng, Z., & Su, J.-C. (2023) · Theranostics · doi:10.7150/thno.78639 · Cited by 144
“and metalloproteinase with thrombospondin motifs (ADAMTS) family to cleave and disassemble type II collagen and aggrecan in the ECM, thereby destroying cartilage structure [47, 48, 50].”
BackgroundAutophagy: controlling cell fate in rheumatic diseases
Rockel, J. S., & Kapoor, M. (2016) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2016.92 · Cited by 151
Self-citationCellular senescence in musculoskeletal homeostasis, diseases, and regeneration
Wan, M., Gray-Gaillard, E. F., & Elisseeff, J. H. (2021) · Bone Research · doi:10.1038/s41413-021-00164-y · Cited by 155
“(MMP)-13 and aggrecan-degrading ADAMTS-5.(114,115) In addition, oxidative stress promotes chondrocyte senescence, mainly by activating p38 MAPK and PI3K/Akt signaling, leading to SASP factor production and increased inflammation and tissue deterioration.”
BackgroundWoodell-May, J. E., Matuska, A., Oyster, M., Welch, Z. R., O'shaughnessey, K., & Hoeppner, J. (2011) · Journal of Orthopaedic Research · doi:10.1002/jor.21384 · Cited by 143
“The APS preparations used in this study were generated from healthy donors who did not have OA.”
BackgroundInfluentiallnc RNA s: novel players in intervertebral disc degeneration and osteoarthritis
Chen, W., Yu, X., Yang, W. Y., Wang, C., He, W., Yan, Y., Zhang, J., & Wang, W. (2016) · Cell Proliferation · doi:10.1111/cpr.12313 · Cited by 136
Yin, K.-J., Huang, J.-X., Wang, P., Yang, X., Tao, S., Li, H., Ni, J., & Pan, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.808832 · Cited by 187
“OA is a whole-joint disease characterized by articular cartilage loss and alterations in the subchondral bone (5).”
BackgroundNisar, A., Jagtap, S., Vyavahare, S., Deshpande, M., Harsulkar, A., Ranjekar, P. K., & Prakash, O. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1177050 · Cited by 183
“Once thought to be cartilage-driven, OA is characterized by inflammatory synovium (Goldring and Otero, 2011; Kapoor et al., 2011; Loeser et al., 2012).”
BackgroundThe Crosstalk Between Hippo-YAP Pathway and Innate Immunity
Wang, S., Zhou, L., Ling, L., Meng, X., Chu, F., Zhang, S., & Zhou, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00323 · Cited by 143
“NDR2 deficiency increased IL-17induced IL-6, CXCL2 and CCL20 expression (85) (Figure 4).”
BackgroundInfluentialLiao, C., Wang, S., Zhu, S., Wang, Y., Li, Z., Liu, Z., Jiang, W., Chen, J., & Wu, Q. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101306 · Cited by 152
“Levels of TNF-α and IL-1β are remarkably increased in OA patients compared to healthy individuals [10].”
BackgroundEymard, F., Pigenet, A., Citadelle, D., Flouzat-Lachaniette, C., Poignard, A., Benelli, C., Berenbaum, F., Chevalier, X., & Houard, X. (2014) · Arthritis & Rheumatology · doi:10.1002/art.38657 · Cited by 136
Role of the inflammation-autophagy-senescence integrative network in osteoarthritis
Vinatier, C., Domínguez, E., Guicheux, J., & Caramés, B. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00706 · Cited by 135
Chemistry, pharmacokinetics, pharmacological activities, and toxicity of Quercitrin
Chen, J., Li, G., Sun, C., Peng, F., Yu, L., Chen, Y., Tan, Y., Cao, X., Tang, Y., Xie, X., et al. (2022) · Phytotherapy Research · doi:10.1002/ptr.7397 · Cited by 143
Tian, F., Wang, J.-H., Zhang, Z., & Yang, J. (2020) · Biological Research · doi:10.1186/s40659-020-00275-6 · Cited by 134
“It has been previously reported that cellular inflammatory factors are widely involved in the pathogenesis of OA [6].”
BackgroundImmunomodulatory Functions of Mesenchymal Stem Cells in Tissue Engineering
Li, H., Shen, S. H., Fu, H., Wang, Z., Li, X., Sui, X., Yuan, M., Liu, S., Wang, G., & Guo, Q. (2019) · Stem Cells International · doi:10.1155/2019/9671206 · Cited by 151
“IL-1 induces the release of proinflammatory cytokines, such as matrix metalloproteinases (MMPs) and NO, and downregulates the expression of primary extracellular matrix (ECM) components to promote catabolism and antisynthesis in the metabolic signaling of articular chondrocytes [72, 73].”
BackgroundChen, J., Xie, J.-J., Shi, K.-S., Gu, Y.-T., Wu, C.-C., Xuan, J., Ren, Y., Chen, L., Wu, Y.-S., Zhang, X.-L., et al. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0217-y · Cited by 130
Intracellular trafficking and secretion of inflammatory cytokines
Stow, J. L., & Murray, R. Z. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.04.001 · Cited by 128
“The proinflammatory cytokine TNF, through its secretion and subsequent binding to TNF receptors located on the surface of many different cell types, is a key driver of inflammation and plays a major role in the pathogenesis of many chronic inflammatory diseases [6,73].”
BackgroundInfluentialMalemud, C. (2018) · Cells · doi:10.3390/cells7080092 · Cited by 128
Pearson, M., Philp, A. M., Heward, J., Roux, B., Walsh, D., Davis, E., Lindsay, M., & Jones, S. W. (2016) · Arthritis & Rheumatology · doi:10.1002/art.39520 · Cited by 128
“compared to normal healthy joints (9), and cytokine stimulation of ex vivo cartilage tissue mimics the pathologic changes observed within the OA joint (9,10).”
BackgroundKey cell signaling pathways modulated by zerumbone: Role in the prevention and treatment of cancer
Prasannan, R., Kalesh, K., Shanmugam, M. K., Nachiyappan, A., Ramachandran, L., Nguyen, A. H., Kumar, A. P., Lakshmanan, M., Ahn, K. S., & Sethi, G. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.07.015 · Cited by 136
Stem Cell-Based Microphysiological Osteochondral System to Model Tissue Response to Interleukin-1β
Lin, H., Lozito, T. P., Alexander, P., Gottardi, R., & Tuan, R. (2014) · Molecular Pharmaceutics · doi:10.1021/mp500136b · Cited by 127
Hong, Y.-O.-S., Moon, S.-J., Joo, Y.-B., Jeon, C., Cho, M., Ju, J., Oh, H., Heo, Y.-J., Park, S.-H., Kim, H.-Y., et al. (2011) · Journal of Korean medical science · doi:10.3346/jkms.2011.26.9.1132 · Cited by 127
“IL-1β, TNF and IL-6 seem to be the main proinflammatory cytokines involved in the pathophysiology of OA (19).”
BackgroundThe role of the immune system in osteoarthritis: mechanisms, challenges and future directions
Moulin, D., Sellam, J., Berenbaum, F., Guicheux, J., & Boutet, M. (2025) · Nature Reviews Rheumatology · doi:10.1038/s41584-025-01223-y · Cited by 136
“Indeed, B cells can directly or indirectly promote the production of MMPs and aggrecanases (ADAMTS), which leads to the breakdown of cartilage 74 .”
Bajpayee, A., Quadir, M. A., Hammond, P. T., & Grodzinsky, A. (2015) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2015.07.010 · Cited by 125
Zhang, B., Chen, H., Ouyang, J., Xie, Y., Chen, L., Tan, Q., Du, X., Su, N. Y., Ni, Z., & Chen, L. (2019) · Autophagy · doi:10.1080/15548627.2019.1664705 · Cited by 135
“Moreover, many inflammatory mediators are detected in synovial fluid and synovial membrane of OA patients [4].”
BackgroundThe Importance of Subchondral Bone in the Pathophysiology of Osteoarthritis
Stewart, H., & Kawcak, C. (2018) · Frontiers in Veterinary Science · doi:10.3389/fvets.2018.00178 · Cited by 124
“For example, sclerosis reduces the shock-absorbing capability of the subchondral bone, and increases the risk of shear-induced tensile failure of the articular cartilage cross-links (12); and subchondral bone has also been demonstrated as a potential source of inflammatory mediators that have been associated with degr…”
BackgroundHwang, J. J., Rim, Y. A., Nam, Y., & Ju, J. H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.631291 · Cited by 148
Kang, M.-L., Kim, J.-E., & Im, G. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.05.005 · Cited by 122
Wang, C., Gao, Y., Zhang, Z., Chi, Q., Liu, Y., Yang, L., & Xu, K. (2020) · Phytomedicine · doi:10.1016/j.phymed.2020.153305 · Cited by 120
Therapeutics in Osteoarthritis Based on an Understanding of Its Molecular Pathogenesis
Kim, J., Yoo, J. J., & Kim, H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030674 · Cited by 139
“It also acts synergistically with other cytokines, IL-6 and chemokines including IL-8, MCP-1, and CCL5, to further increase inflammation [14].”
BackgroundBastos, R., Mathias, M., Andrade, R., Amaral, R. J. F. C., Schott, V., Balduino, A., Bastos, R., Miguel Oliveira, J., Reis, R. L., Rodeo, S., et al. (2020) · Knee Surgery, Sports Traumatology, Arthroscopy · doi:10.1007/s00167-019-05732-8 · Cited by 117
Yu, H., Huang, T., Lu, W. W., Tong, L., & Chen, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094642 · Cited by 157
“IL-1β is the other important proinflammatory cytokine involved in the chronic and lowgrade inflammation in OA pathophysiology [35].”
BackgroundLi, Y.-H., Tavallaee, G., Tokár, T., Nakamura, A., Sundararajan, K., Weston, A., Sharma, A., Mahomed, N. N., Gandhi, R., Jurišica, I., et al. (2016) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2016.04.019 · Cited by 113
Self-citationBoehme, K. A., & Rolauffs, B. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082282 · Cited by 114
“Although human healthy and OA SF contains about 20 pg/mL IL-1β and less than 3 ng/mL TNF-α, many studies using inflammatory cytokines for experimental OA induction apply apparently supra-physiological doses of 1–100 ng/mL rIL-1β and up to 50 ng/mL rTNF-α for activation of downstream signaling [21,125], which may proba…”
BackgroundInfluentialmicroRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints
Nakamura, A., Rampersaud, Y. R., Nakamura, S., Sharma, A., Zeng, F., Rossomacha, E., Ali, S. A., Krawetz, R. J., Haroon, N., Perruccio, A. V., et al. (2018) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2018-213629 · Cited by 117
Self-citationSacitharan, P. K. (2019) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-3681-2_6 · Cited by 316
Regulation and therapy, the role of JAK2/STAT3 signaling pathway in OA: a systematic review
Chen, B., Ning, K., Sun, M., & Zhang, X. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01094-4 · Cited by 117
“During the progression of OA, large amounts of inflammatory factors (IL-1β, IL-6, TNF-α, and IL-8) produced in chondrocytes or synovial cells can accelerate cartilage degradation [37].”
BackgroundClassification of four distinct osteoarthritis subtypes with a knee joint tissue transcriptome atlas
Yuan, C., Pan, Z., Zhao, K., Li, J., Sheng, Z., Yao, X., Liu, H., Zhang, X., Yang, Y., Yu, D., et al. (2020) · Bone Research · doi:10.1038/s41413-020-00109-x · Cited by 127
“IFNγ and IL6 are cytokines with essential immunoregulatory functions.(20,21) Our ELISA results showed higher expression of IFNγ in C1, VEGFA and IL6 in C2, and MIP1α, SDF1α, and IL8 in C4 (Fig.”
BackgroundJin, Z. X., Ren, J., & Qi, S. (2020) · Cell and Tissue Research · doi:10.1007/s00441-020-03193-x · Cited by 125
“The progression of OA shares a close association with progressive destruction of articular cartilage, remodeling of subchondral bone and inflammation of the synovial membrane; however, little is known about the etiology and pathogenesis of OA (Kapoor et al. 2011).”
BackgroundKuah, D., Sivell, S., Longworth, T., James, K., Guermazi, A., Cicuttini, F., Wang, Y., Craig, S., Comin, G., Robinson, D. S., et al. (2018) · Journal of Translational Medicine · doi:10.1186/s12967-018-1420-z · Cited by 119
“Analgesics and NSAIDs are typical first-line treatments used for symptom relief in OA patients [34, 35].”
BackgroundWu, Y., Zhang, Y., Zhang, Y. X., & Wang, J. (2017) · Cell Biology International · doi:10.1002/cbin.10761 · Cited by 123
“IL-1b is an initial factor for inflammatory response regulation during the pathogenesis of OA (Kapoor et al., 2011).”
BackgroundAini, H., Itaka, K., Fujisawa, A., Uchida, H., Uchida, S., Fukushima, S., Kataoka, K., Saito, T., Chung, U., & Ohba, S. (2016) · Scientific Reports · doi:10.1038/srep18743 · Cited by 112
Moilanen, L. J., Hämäläinen, M., Nummenmaa, E., Ilmarinen, P., Vuolteenaho, K., Nieminen, R., Lehtimäki, L., & Moilanen, E. (2015) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2015.09.008 · Cited by 112
Matrix cross-linking–mediated mechanotransduction promotes posttraumatic osteoarthritis
Kim, J.-H., Lee, G., Won, Y., Lee, M.-J., Kwak, J.-S., Chun, C.-H., & Chun, J.-S. (2015) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1505700112 · Cited by 112
“Indeed, both HSF1 and NF-κB are implicated in inflammatory arthritis, and their activation by proinflammatory cytokines is well documented (25, 26).”
BackgroundLaiguillon, M.-C., Houard, X., Bougault, C., Gosset, M., Nourissat, G., Sautet, A., Jacques, C., Berenbaum, F., & Sellam, J. (2014) · Arthritis Research & Therapy · doi:10.1186/ar4467 · Cited by 123
“All of these cells produce interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor alpha (TNFα), major proinflammatory cytokines in OA [3,4].”
BackgroundXue, C., Tian, J., Cui, Z., Liu, Y., Sun, D., Xiong, M.-T., Yi, N., Wang, K.-Q., Li, X.-F., Wang, Y.-J., et al. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.10.032 · Cited by 111
“Increasing evidence has been revealed that synovial inflammation pre-cedes cartilage degeneration [6,7].”
BackgroundTissue-engineered cartilage with inducible and tunable immunomodulatory properties
Glass, K. A., Link, J. M., Brunger, J. M., Moutos, F. T., Gersbach, C., & Guilak, F. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.03.073 · Cited by 111
“expression of primary extracellular matrix (ECM) components including type II collagen and aggrecan [11,12].”
Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?
van den Bosch, M. H. J. (2018) · Clinical & Experimental Immunology · doi:10.1111/cei.13237 · Cited by 137
Platelet-Rich Plasma and Cartilage Repair
Kennedy, M. I., Whitney, K. E., Evans, T. A., & LaPrade, R. F. (2018) · Current Reviews in Musculoskeletal Medicine · doi:10.1007/s12178-018-9516-x · Cited by 124
Schell, J., Scofield, R., Barrett, J., Kurien, B., Betts, N., Lyons, T., Zhao, Y. D., & Basu, A. (2017) · Nutrients · doi:10.3390/nu9090949 · Cited by 110
“Multiple cytokines and inflammatory molecules, especially CRP, IL-6, and IL-1β, and free radicals, such as nitric oxide, are implicated in the progression of OA [38,39].”
BackgroundLi, Y., Zhang, F., Zeng, C., Luo, W., Xiao, W., Gao, S., & Lei, G. (2015) · Joint Bone Spine · doi:10.1016/j.jbspin.2015.06.009 · Cited by 146
The inflammatory circuitry of miR-149 as a pathological mechanism in osteoarthritis
Santini, P., Politi, L., Vedova, P. D., Scandurra, R., & d'Abusco, A. S. (2014) · Rheumatology International · doi:10.1007/s00296-013-2754-8 · Cited by 110
“Moreover, they amplify the inflammatory process, mainly through transcriptional activation of cytokine genes [13].”
BackgroundStrategies to Target ADAM17 in Disease: From Its Discovery to the iRhom Revolution
Calligaris, M., Cuffaro, D., Bonelli, S., Spanò, D. P., Rossello, A., Nuti, E., & Scilabra, S. D. (2021) · Molecules · doi:10.3390/molecules26040944 · Cited by 123
“Nevertheless, synovial macrophages that release proinflammatory cytokines, especially TNF, are acknowledged to be implicated in the pathological chain of events eventually leading to deterioration of cartilage in the joint, which is a hallmark of the disease [106].”
BackgroundA Dual Role for NOTCH Signaling in Joint Cartilage Maintenance and Osteoarthritis
Liu, Z.-Y., Chen, J.-Q., Mirando, A. J., Wang, C.-C., Zuscik, M., O'Keefe, R., & Hilton, M. J. (2015) · Science Signaling · doi:10.1126/scisignal.aaa3792 · Cited by 109
“Real-time qPCR analysis demonstrated that by the age of 2 months, the expression of Sox9, Col2a1, and Acan was substantially increased (between two- and threefold for each) in tGOF NICD1 mutant mice, whereas the expression of Col10a1 was decreased by more than twofold.”
BackgroundInfluentialMicroRNA‐34a‐5p Promotes Joint Destruction During Osteoarthritis
Endisha, H., Datta, P., Sharma, A., Nakamura, S., Rossomacha, E., Younan, C., Ali, S., Tavallaee, G., Lively, S., Potla, P., et al. (2020) · Arthritis & Rheumatology · doi:10.1002/art.41552 · Cited by 108
“Following treatment with mimic or ASO, expression levels of key proinflammatory cytokines (TNF and IL6), a profibrotic cytokine (transforming growth factor β [TGFβ]), a key ECM marker (COL1A1), a myofibroblast marker (α-smooth muscle actin [α-SMA], encoded by ACTA2 gene), and autophagy markers (ATG5, ATG3, and ULK1) w…”
Self-citationZ-ligustilide: A review of its pharmacokinetics and pharmacology.
Xie, Q., Zhang, L., Xie, L., Zheng, Y., Liu, K., Tang, H., Liao, Y., & Li, X. (2020) · Phytotherapy Research · doi:10.1002/ptr.6662 · Cited by 108
Kroon, F. P. B., Kortekaas, M. C., Boonen, A. E. R. C. H., Böhringer, S., Reijnierse, M., Rosendaal, F. R., Riyazi, N., Starmans, M., Turkstra, F., van Zeben, J., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)32489-4 · Cited by 130
Hu, G., Zhao, X.-Y., Wang, C.-D., Geng, Y.-Y., Zhao, J.-Y., Xu, J.-J., Zuo, B., Zhao, C., Wang, C.-L., & Zhang, X.-L. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.522 · Cited by 108
“In turn, miR-145 suppresses TNF-α-mediated JNK/c-Jun and p38/ATF2 activation and induction of MMP-3, MMP-13, and Adamts-5 by directly targeting mitogenactivated protein kinase kinase 4 (MKK4), and consequently attenuates cartilage matrix degradation in experimental OA.”
BackgroundInfluentialLi, Y., Wang, Y., Chubinskaya, S., Schoeberl, B., Florine, E., Kopesky, P., & Grodzinsky, A. (2014) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2014.11.006 · Cited by 108
The role of resilience in the clinical management of chronic pain
Hassett, A. L., & Finan, P. H. (2016) · Current Pain and Headache Reports · doi:10.1007/s11916-016-0567-7 · Cited by 107
Moutos, F. T., Glass, K. A., Compton, S. A., Ross, A. K., Gersbach, C., Guilak, F., & Estes, B. (2016) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1601639113 · Cited by 107
Ongaro, A., Varani, K., Masieri, F., Pellati, A., Massari, L., Cadossi, R., Vincenzi, F., Borea, P., Fini, M., Caruso, A., et al. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.22981 · Cited by 107
“From this background, the first aim of this study was to investigate whether EMFs might modulate inflammatory activities of humanOASFs in the absence and in the presence of IL-1b, the main cytokine involved in OA (Kapoor et al., 2011).”
BackgroundResultRasheed, Z., Rasheed, N., Abdulmonem, W. A., & Khan, M. I. (2019) · Scientific Reports · doi:10.1038/s41598-019-42601-3 · Cited by 106
Malekpour, K., Hazrati, A., Zahar, M., Markov, A. A., Zekiy, A. O., Navashenaq, J. G., Roshangar, L., & Ahmadi, M. (2021) · Stem Cell Reviews and Reports · doi:10.1007/s12015-021-10185-z · Cited by 120
“In OA pathology, pro-inflammatory cytokines and matrix metalloproteinases (MMPs) [116] are mainly produced by the synovium and immune cells, such as macrophages, and play a role in the initiation and progression of OA.”
BackgroundEpigenetic regulation of interleukin-8, an inflammatory chemokine, in osteoarthritis
Takahashi, A., de Andrés, M. C., Hashimoto, K., Itoi, E., & Oreffo, R. O. C. (2015) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2015.02.168 · Cited by 113
A Brief Overview: Sex Differences in Prevalent Chronic Musculoskeletal Conditions
Overstreet, D., Strath, L. J., Jordan, M., Jordan, I. A., Hobson, J., Owens, M., Williams, A. C., Edwards, R., & Meints, S. M. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20054521 · Cited by 104
“A greater concentration of immune markers such as pro-inflammatory cytokines have been reported in cLBP [42] much like other MSK disorders such as osteoarthritic disease [43].”
BackgroundPost-traumatic osteoarthritis: A review of pathogenic mechanisms and novel targets for mitigation
Dilley, J. E., Bello, M., Natoli, R. M., McKinley, T. O., & Sankar, U. (2023) · Bone Reports · doi:10.1016/j.bonr.2023.101658 · Cited by 111
Hou, W., Ye, C., Chen, M., Gao, W., Xie, X., Wu, J., Zhang, K., Zhang, W., Zheng, Y., & Cai, X. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.01.016 · Cited by 109
“When chondrocytes are stimulated by IL-1β, they age rapidly or undergo apoptosis [61].”
BackgroundArtificial M2 macrophages for disease-modifying osteoarthritis therapeutics.
Ma, Y., Yang, H., Zong, X., Wu, J., Ji, X., Liu, W., Yuan, P., Chen, X., Yang, C., Li, X.-D., et al. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120865 · Cited by 103
Strategies for Controlled Delivery of Biologics for Cartilage Repair
Lam, J., Lu, S., Kasper, F., & Mikos, A. G. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.06.006 · Cited by 103
“In addition to palliative treatments, antiinflammatory agents have also been delivered through intra-articular means to treat OA inflammation [77-79].”
BackgroundThe role of miR‐29 family in disease
Horita, M., Farquharson, C., & Stephen, L. A. (2021) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29896 · Cited by 113
“How miR‐29s contribute to cartilage destruction in OA is unclear but their involvement may be linked to the actions of proinflammatory cytokines, such as interleukin‐1 β (IL‐1β) and tumor necrosis factor alpha (TNF‐α), that are released from the synovium and chondrocytes during OA pathogenesis.(59,60) IL‐1β has been r…”
BackgroundOsteoarthritis and inflammation: a serious disease with overlapping phenotypic patterns
Berenbaum, F., & Walker, C. (2020) · Postgraduate Medicine · doi:10.1080/00325481.2020.1730669 · Cited by 113
“tissues, contribute to OA pathophysiology, which control degeneration of the articular cartilage matrix [22].”
BackgroundBench-to-bedside strategies for osteoporotic fracture: From osteoimmunology to mechanosensation
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Retracted
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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