Role of proinflammatory cytokines in the pathophysiology of osteoarthritis (original) (raw)

• Felson, D. T. Clinical practice. Osteoarthritis of the knee. N. Engl. J. Med. 354, 841–848 (2006).
  Article CAS PubMed Google Scholar
• Ayral, X., Pickering, E. H., Woodworth, T. G., Mackillop, N. & Dougados, M. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis—results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthritis Cartilage 13, 361–367 (2005).
  Article CAS PubMed Google Scholar
• Pozgan, U. et al. Expression and activity profiling of selected cysteine cathepsins and matrix metalloproteinases in synovial fluids from patients with rheumatoid arthritis and osteoarthritis. Biol. Chem. 391, 571–579 (2010).
  Article CAS PubMed Google Scholar
• Martel-Pelletier, J., Lajeunesse, D. & Pelletier, J. P. in Arthritis and Allied Conditions. A Textbook of Rheumatology 15th edn (eds Koopman, W. J. & Moreland, L. W.) 2199–2226 (Lippincott Williams & Wilkins, Baltimore, USA, 2005).
  Google Scholar
• Page Thomas, D. P., King, B., Stephens, T. & Dingle, J. T. In vivo studies of cartilage regeneration after damage induced by catabolin/interleukin-1. Ann. Rheum. Dis. 50, 75–80 (1991).
  Article CAS PubMed PubMed Central Google Scholar
• Henderson, B. & Pettipher, E. R. Arthritogenic actions of recombinant IL-1 and tumour necrosis factor α in the rabbit: evidence for synergistic interactions between cytokines in vivo. Clin. Exp. Immunol. 75, 306–310 (1989).
  CAS PubMed PubMed Central Google Scholar
• Clements, K. M. et al. Gene deletion of either interleukin-1β, interleukin-1β-converting enzyme, inducible nitric oxide synthase, or stromelysin 1 accelerates the development of knee osteoarthritis in mice after surgical transection of the medial collateral ligament and partial medial meniscectomy. Arthritis Rheum. 48, 3452–3463 (2003).
  Article CAS PubMed Google Scholar
• Arend, W. P. Interleukin-1 receptor antagonist. Adv. Immunol. 54, 167–227 (1993).
  Article CAS PubMed Google Scholar
• Martel-Pelletier, J. et al. The interleukin-1 receptor in normal and osteoarthritic human articular chondrocytes. Identification as the type I receptor and analysis of binding kinetics and biologic function. Arthritis Rheum. 35, 530–540 (1992).
  Article CAS PubMed Google Scholar
• Sadouk, M. B. et al. Human synovial fibroblasts coexpress IL-1 receptor type I and type II mRNA. The increased level of the IL-1 receptor in osteoarthritic cells is related to an increased level of the type I receptor. Lab. Invest. 73, 347–355 (1995).
  CAS PubMed Google Scholar
• Colotta, F., Dower, S. K., Sims, J. E. & Mantovani, A. The type II 'decoy' receptor: a novel regulatory pathway for interleukin 1. Immunol. Today 15, 562–566 (1994).
  Article CAS PubMed Google Scholar
• Palmer, G. et al. Production of interleukin-1 receptor antagonist by human articular chondrocytes. Arthritis Res. 4, 226–231 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Seitz, M. et al. Production of interleukin-1 receptor antagonist, inflammatory chemotactic proteins, and prostaglandin E by rheumatoid and osteoarthritic synoviocytes—regulation by IFN-γ and IL-4. J. Immunol. 152, 2060–2065 (1994).
  CAS PubMed Google Scholar
• Alaaeddine, N. et al. Osteoarthritic synovial fibroblasts possess an increased level of tumor necrosis factor-receptor 55 (TNF-R55) that mediates biological activation by TNFα. J. Rheumatol. 24, 1985–1994 (1997).
  CAS PubMed Google Scholar
• Naume, B., Shalaby, R., Lesslauer, W. & Espevik, T. Involvement of the 55- and 75-kDa tumor necrosis factor receptors in the generation of lymphokine-activated killer cell activity and proliferation of natural killer cells. J. Immunol. 146, 3045–3048 (1991).
  CAS PubMed Google Scholar
• Hohmann, H. P. et al. Expression of the types A and B tumor necrosis factor (TNF) receptors is independently regulated, and both receptors mediate activation of the transcription factor NF-κB. TNFα is not needed for induction of a biological effect via TNF receptors. J. Biol. Chem. 265, 22409–22417 (1990).
  CAS PubMed Google Scholar
• Westacott, C. I., Atkins, R. M., Dieppe, P. A. & Elson, C. J. Tumor necrosis factor α receptor expression on chondrocytes isolated from human articular cartilage. J. Rheumatol. 21, 1710–1715 (1994).
  CAS PubMed Google Scholar
• Saklatvala, J. Tumour necrosis factor α stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature 322, 547–549 (1986).
  Article CAS PubMed PubMed Central Google Scholar
• Goldring, M. B., Fukuo, K., Birkhead, J. R., Dudek, E. & Sandell, L. J. Transcriptional suppression by interleukin-1 and interferon-γ of type II collagen gene expression in human chondrocytes. J. Cell. Biochem. 54, 85–99 (1994).
  Article CAS PubMed Google Scholar
• Chadjichristos, C. et al. Sp1 and Sp3 transcription factors mediate interleukin-1β down-regulation of human type II collagen gene expression in articular chondrocytes. J. Biol. Chem. 278, 39762–39772 (2003).
  Article CAS PubMed Google Scholar
• Shakibaei, M., Schulze-Tanzil, G., John, T. & Mobasheri, A. Curcumin protects human chondrocytes from IL-l1β -induced inhibition of collagen type II and β1-integrin expression and activation of caspase-3: an immunomorphological study. Ann. Anat. 187, 487–497 (2005).
  Article CAS PubMed Google Scholar
• Stöve, J., Huch, K., Günther, K. P. & Scharf, H. P. Interleukin-1β induces different gene expression of stromelysin, aggrecan and tumor-necrosis-factor-stimulated gene 6 in human osteoarthritic chondrocytes in vitro. Pathobiology 68, 144–149 (2000).
  Article PubMed Google Scholar
• Nietfeld, J. J., Wilbrink, B., Den Otter, W., Huber, J. & Huber-Bruning, O. The effect of human interleukin 1 on proteoglycan metabolism in human and porcine cartilage explants. J. Rheumatol. 17, 818–826 (1990).
  CAS PubMed Google Scholar
• Gouze, J. N. et al. Interleukin-1β down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on interleukin-1β-mediated effects in rat chondrocytes. Arthritis Rheum. 44, 351–360 (2001).
  Article CAS PubMed Google Scholar
• Séguin, C. A. & Bernier, S. M. TNFα suppresses link protein and type II collagen expression in chondrocytes: Role of MEK1/2 and NF-κB signaling pathways. J. Cell. Physiol. 197, 356–369 (2003).
  Article CAS PubMed Google Scholar
• Mengshol, J. A., Vincenti, M. P., Coon, C. I., Barchowsky, A. & Brinckerhoff, C. E. Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor κB: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum. 43, 801–811 (2000).
  Article CAS PubMed Google Scholar
• Lefebvre, V., Peeters-Joris, C. & Vaes, G. Modulation by interleukin 1 and tumor necrosis factor α of production of collagenase, tissue inhibitor of metalloproteinases and collagen types in differentiated and dedifferentiated articular chondrocytes. Biochim. Biophys. Acta 1052, 366–378 (1990).
  Article CAS PubMed Google Scholar
• Reboul, P., Pelletier, J. P., Tardif, G., Cloutier, J. M. & Martel-Pelletier, J. The new collagenase, collagenase-3, is expressed and synthesized by human chondrocytes but not by synoviocytes. A role in osteoarthritis. J. Clin. Invest. 97, 2011–2019 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Glasson, S. S. et al. Characterization of and osteoarthritis susceptibility in ADAMTS-4-knockout mice. Arthritis Rheum. 50, 2547–2558 (2004).
  Article CAS PubMed Google Scholar
• Glasson, S. S. et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 434, 644–648 (2005).
  Article CAS PubMed Google Scholar
• Tortorella, M. D., Malfait, A. M., Deccico, C. & Arner, E. The role of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) in a model of cartilage degradation. Osteoarthritis Cartilage 9, 539–552 (2001).
  Article CAS PubMed Google Scholar
• Bondeson, J., Wainwright, S. D., Lauder, S., Amos, N. & Hughes, C. E. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Res. Ther. 8, R187 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Guerne, P. A., Carson, D. A. & Lotz, M. IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J. Immunol. 144, 499–505 (1990).
  CAS PubMed Google Scholar
• Lotz, M., Terkeltaub, R. & Villiger, P. M. Cartilage and joint inflammation. Regulation of IL-8 expression by human articular chondrocytes. J. Immunol. 148, 466–473 (1992).
  CAS PubMed Google Scholar
• Villiger, P. M., Terkeltaub, R. & Lotz, M. Monocyte chemoattractant protein-1 (MCP-1) expression in human articular cartilage. Induction by peptide regulatory factors and differential effects of dexamethasone and retinoic acid. J. Clin. Invest. 90, 488–496 (1992).
  Article CAS PubMed PubMed Central Google Scholar
• Alaaeddine, N., Olee, T., Hashimoto, S., Creighton-Achermann, L. & Lotz, M. Production of the chemokine RANTES by articular chondrocytes and role in cartilage degradation. Arthritis Rheum. 44, 1633–1643 (2001).
  Article CAS PubMed Google Scholar
• Afonso, V., Champy, R., Mitrovic, D., Collin, P. & Lomri, A. Reactive oxygen species and superoxide dismutases: role in joint diseases. Joint Bone Spine 74, 324–329 (2007).
  Article CAS PubMed Google Scholar
• Mathy-Hartert, M. et al. Interleukin-1β and interleukin-6 disturb the antioxidant enzyme system in bovine chondrocytes: a possible explanation for oxidative stress generation. Osteoarthritis Cartilage 16, 756–763 (2008).
  Article CAS PubMed Google Scholar
• Scott, J. L. et al. Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease. Ann. Rheum. Dis. 69, 1502–1510 (2010).
  Article CAS PubMed Google Scholar
• Roman-Blas, J. A. & Jimenez, S. A. NF-κB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage 14, 839–848 (2006).
  Article CAS PubMed Google Scholar
• Chen, L. X. et al. Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-κBp65-specific siRNA. Osteoarthritis Cartilage 16, 174–184 (2008).
  Article CAS PubMed Google Scholar
• Blom, A. B. et al. Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum. 60, 501–512 (2009).
  Article CAS PubMed Google Scholar
• Yuasa, T., Otani, T., Koike, T., Iwamoto, M. & Enomoto-Iwamoto, M. Wnt/β-catenin signaling stimulates matrix catabolic genes and activity in articular chondrocytes: its possible role in joint degeneration. Lab. Invest. 88, 264–274 (2008).
  Article CAS PubMed Google Scholar
• Lane, N. E., Nevitt, M. C., Lui, L. Y., de Leon, P. & Corr, M. Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly Caucasian women. Arthritis Rheum. 56, 3319–3325 (2007).
  Article CAS PubMed Google Scholar
• Fahmi, H., Pelletier, J. P. & Martel-Pelletier, J. PPARg ligands as modulators of inflammatory and catabolic responses in arthritis. An overview. J. Rheumatol. 29, 3–14 (2002).
  CAS PubMed Google Scholar
• Kobayashi, T. et al. Pioglitazone, a peroxisome proliferator-activated receptor γ agonist, reduces the progression of experimental osteoarthritis in guinea pigs. Arthritis Rheum. 52, 479–487 (2005).
  Article CAS PubMed Google Scholar
• Boileau, C. et al. The peroxisome proliferator-activated receptor γ agonist pioglitazone reduces the development of cartilage lesions in an experimental dog model of osteoarthritis: in vivo protective effects mediated through the inhibition of key signaling and catabolic pathways. Arthritis Rheum. 56, 2288–2298 (2007).
  Article CAS PubMed Google Scholar
• Kobayashi, M. et al. Role of interleukin-1 and tumor necrosis factor α in matrix degradation of human osteoarthritic cartilage. Arthritis Rheum. 52, 128–135 (2005).
  Article CAS PubMed Google Scholar
• Caron, J. P. et al. Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis. Suppression of collagenase-1 expression. Arthritis Rheum. 39, 1535–1544 (1996).
  Article CAS PubMed Google Scholar
• Pelletier, J. P. et al. In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum. 40, 1012–1019 (1997).
  Article CAS PubMed Google Scholar
• Fernandes, J. et al . In vivo transfer of interleukin-1 receptor antagonist gene in osteoarthritic rabbit knee joints: prevention of osteoarthritis progression. Am. J. Pathol. 154, 1159–1169 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, X., Mao, Z. & Yu, C. Suppression of early experimental osteoarthritis by gene transfer of interleukin-1 receptor antagonist and interleukin-10. J. Orthop. Res. 22, 742–750 (2004).
  Article CAS PubMed Google Scholar
• Frisbie, D. D., Ghivizzani, S. C., Robbins, P. D., Evans, C. H. & McIlwraith, C. W. Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene. Gene Ther. 9, 12–20 (2002).
  Article CAS PubMed Google Scholar
• Chevalier, X. et al. Safety study of intraarticular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis: a multicenter study. J. Rheumatol. 32, 1317–1323 (2005).
  CAS PubMed Google Scholar
• Chevalier, X. et al. Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 61, 344–352 (2009).
  Article CAS PubMed Google Scholar
• Bacconnier, L., Jorgensen, C. & Fabre, S. Erosive osteoarthritis of the hand: clinical experience with anakinra. Ann. Rheum. Dis. 68, 1078–1079 (2009).
  Article CAS PubMed Google Scholar
• Attur, M. G. et al. Functional genomic analysis of type II IL-1β decoy receptor: potential for gene therapy in human arthritis and inflammation. J. Immunol. 168, 2001–2010 (2002).
  Article CAS PubMed Google Scholar
• Grunke, M. & Schulze-Koops, H. Successful treatment of inflammatory knee osteoarthritis with tumour necrosis factor blockade. Ann. Rheum. Dis. 65, 555–556 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Fioravanti, A., Fabbroni, M., Cerase, A. & Galeazzi, M. Treatment of erosive osteoarthritis of the hands by intra-articular infliximab injections: a pilot study. Rheumatol. Int. 29, 961–965 (2009).
  Article CAS PubMed Google Scholar
• Magnano, M. D. et al. A pilot study of tumor necrosis factor inhibition in erosive/inflammatory osteoarthritis of the hands. J. Rheumatol. 34, 1323–1327 (2007).
  CAS PubMed Google Scholar
• Efficacy study of an anti-tumor necrosis factor (TNF)-α agent in patients with hand osteoarthritis (DORA). http://clinicaltrials.gov [online], (2010).
• Skiles, J. W., Gonnella, N. C. & Jeng, A. Y. The design, structure, and clinical update of small molecular weight matrix metalloproteinase inhibitors. Curr. Med. Chem. 11, 2911–2977 (2004).
  Article CAS PubMed Google Scholar
• Wojtowicz-Praga, S. et al. Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer. J. Clin. Oncol. 16, 2150–2156 (1998).
  Article CAS PubMed Google Scholar
• Murphy, G. & Nagase, H. Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nat. Clin. Pract. Rheumatol. 4, 128–135 (2008).
  Article CAS PubMed Google Scholar
• Krzeski, P. et al. Development of musculoskeletal toxicity without clear benefit after administration of PG-116800, a matrix metalloproteinase inhibitor, to patients with knee osteoarthritis: a randomized, 12-month, double-blind, placebo-controlled study. Arthritis Res. Ther. 9, R109 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Clutterbuck, A. L., Asplin, K. E., Harris, P., Allaway, D. & Mobasheri, A. Targeting matrix metalloproteinases in inflammatory conditions. Curr. Drug Targets 10, 1245–1254 (2009).
  Article CAS PubMed Google Scholar
• Johnson, A. R. et al. Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects. J. Biol. Chem. 282, 27781–27791 (2007).
  Article CAS PubMed Google Scholar
• Tortorella, M. D., Malfait, F., Barve, R. A., Shieh, H. S. & Malfait, A. M. A review of the ADAMTS family, pharmaceutical targets of the future. Curr. Pharm. Des. 15, 2359–2374 (2009).
  Article CAS PubMed Google Scholar
• Marcu, K. B., Otero, M., Olivotto, E., Borzi, R. M. & Goldring, M. B. NF-κB signaling: multiple angles to target OA. Curr. Drug Targets 11, 599–613 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Wegenka, U. M., Buschmann, J., Lütticken, C., Heinrich, P. C. & Horn, F. Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level. Mol. Cell. Biol. 13, 276–288 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Zhong, Z., Wen, Z. & Darnell, J. E. Jr. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264, 95–98 (1994).
  Article CAS PubMed Google Scholar
• Bender, S. et al. Interleukin-1β induces synthesis and secretion of interleukin-6 in human chondrocytes. FEBS Lett. 263, 321–324 (1990).
  Article CAS PubMed Google Scholar
• Wang, P., Zhu, F. & Konstantopoulos, K. Prostaglandin E2 induces interleukin-6 expression in human chondrocytes via cAMP/protein kinase A- and phosphatidylinositol 3-kinase-dependent NF-κB activation. Am. J. Physiol. Cell Physiol. 298, C1445–C1456 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, P., Zhu, F., Lee, N. H. & Konstantopoulos, K. Shear-induced interleukin-6 synthesis in chondrocytes: roles of E prostanoid (EP) 2 and EP3 in cAMP/protein kinase A- and PI3-K/Akt-dependent NF-κB activation. J. Biol. Chem. 285, 24793–24804 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Steensberg, A., Fischer, C. P., Keller, C., Møller, K. & Pedersen, B. K. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am. J. Physiol. Endocrinol. Metab. 285, E433–E437 (2003).
  Article CAS PubMed Google Scholar
• Haider, D. G. et al. C-reactive protein is expressed and secreted by peripheral blood mononuclear cells. Clin. Exp. Immunol. 146, 533–539 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Pearle, A. D. et al. Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthritis Cartilage 15, 516–523 (2007).
  Article CAS PubMed Google Scholar
• Pelletier, J. P. et al. Decrease in serum level of matrix metalloproteinases is predictive of the disease-modifying effect of osteoarthritis drugs assessed by quantitative MRI in patients with knee osteoarthritis. Ann. Rheum. Dis. doi:10.1136/ard.2009.122002.
• Kugisaki, H. et al. Serum concentrations of interleukin-6 in patients following unilateral versus bilateral total knee arthroplasty. J. Orthop. Sci. 14, 437–442 (2009).
  Article CAS PubMed Google Scholar
• Livshits, G. et al. Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: The Chingford Study. Arthritis Rheum. 60, 2037–2045 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Kaneko, S. et al. Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis. Cytokines Cell. Mol. Ther. 6, 71–79 (2000).
  Article CAS PubMed Google Scholar
• Cawston, T. E. et al. The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint. Arthritis Rheum. 41, 1760–1771 (1998).
  Article CAS PubMed Google Scholar
• Rowan, A. D. et al. Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum. 44, 1620–1632 (2001).
  Article CAS PubMed Google Scholar
• Sui, Y. et al. Mechanical injury potentiates proteoglycan catabolism induced by interleukin-6 with soluble interleukin-6 receptor and tumor necrosis factor α in immature bovine and adult human articular cartilage. Arthritis Rheum. 60, 2985–2996 (2009).
  Article CAS PubMed Google Scholar
• Porée, B. et al. Interleukin-6 (IL-6) and/or soluble IL-6 receptor down-regulation of human type II collagen gene expression in articular chondrocytes requires a decrease of Sp1.Sp3 ratio and of the binding activity of both factors to the COL2A1 promoter. J. Biol. Chem. 283, 4850–4865 (2008).
  Article CAS PubMed Google Scholar
• Alonzi, T. et al. Interleukin 6 is required for the development of collagen-induced arthritis. J. Exp. Med. 187, 461–468 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• van de Loo, F. A., Kuiper, S., van Enckevort, F. H., Arntz, O. J. & van den Berg, W. B. Interleukin-6 reduces cartilage destruction during experimental arthritis. A study in interleukin-6-deficient mice. Am. J. Pathol. 151, 177–191 (1997).
  CAS PubMed PubMed Central Google Scholar
• de Hooge, A. S. et al. Male IL-6 gene knock out mice developed more advanced osteoarthritis upon aging. Osteoarthritis Cartilage 13, 66–73 (2005).
  Article PubMed Google Scholar
• Tilg, H., Dinarello, C. A. & Mier, J. W. IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. Immunol. Today 18, 428–432 (1997).
  Article CAS PubMed Google Scholar
• Kwan Tat, S., Padrines, M., Théoleyre, S., Heymann, D. & Fortun, Y. IL-6, RANKL, TNFα/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 15, 49–60 (2004).
  Article CAS PubMed Google Scholar
• Liu, X. H., Kirschenbaum, A., Yao, S. & Levine, A. C. The role of the interleukin-6/gp130 signaling pathway in bone metabolism. Vitam. Horm. 74, 341–355 (2006).
  Article CAS PubMed Google Scholar
• Massicotte, F. et al. Can altered production of interleukin-1β, interleukin-6, transforming growth factor β and prostaglandin E(2) by isolated human subchondral osteoblasts identify two subgroups of osteoarthritic patients. Osteoarthritis Cartilage 10, 491–500 (2002).
  Article CAS PubMed Google Scholar
• Kwan Tat, S. et al. The differential expression of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in human osteoarthritic subchondral bone osteoblasts is an indicator of the metabolic state of these disease cells. Clin. Exp. Rheumatol. 26, 295–304 (2008).
  CAS PubMed Google Scholar
• Chenoufi, H. L. et al. Increased mRNA expression and protein secretion of interleukin-6 in primary human osteoblasts differentiated in vitro from rheumatoid and osteoarthritic bone. J. Cell. Biochem. 81, 666–678 (2001).
  Article CAS PubMed Google Scholar
• Jochems, C., Lagerquist, M., Håkansson, C., Ohlsson, C. & Carlsten, H. Long-term anti-arthritic and anti-osteoporotic effects of raloxifene in established experimental postmenopausal polyarthritis. Clin. Exp. Immunol. 152, 593–597 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Genovese, M. C. et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 58, 2968–2980 (2008).
  Article CAS PubMed Google Scholar
• Smolen, J. S. et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 371, 987–997 (2008).
  Article CAS PubMed Google Scholar
• Garnero, P., Thompson, E., Woodworth, T. & Smolen, J. S. Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum. 62, 33–43 (2010).
  Article CAS PubMed Google Scholar
• Doschak, M. R., Wohl, G. R., Hanley, D. A., Bray, R. C. & Zernicke, R. F. Antiresorptive therapy conserves some periarticular bone and ligament mechanical properties after anterior cruciate ligament disruption in the rabbit knee. J. Orthop. Res. 22, 942–948 (2004).
  Article CAS PubMed Google Scholar
• Jones, M. D. et al. In vivo microfocal computed tomography and micro-magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat. Arthritis Rheum. 62, 2726–2735 (2010).
  Article PubMed Google Scholar
• Bingham, C. O. 3rd et al. Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum. 54, 3494–3507 (2006).
  Article CAS PubMed Google Scholar
• Garnero, P. et al. Relationships between biochemical markers of bone and cartilage degradation with radiological progression in patients with knee osteoarthritis receiving risedronate: the Knee Osteoarthritis Structural Arthritis randomized clinical trial. Osteoarthritis Cartilage 16, 660–666 (2008).
  Article CAS PubMed Google Scholar
• Raynauld, J. P. et al. Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI. Ann. Rheum. Dis. 68, 938–947 (2009).
  Article CAS PubMed Google Scholar
• Scanzello, C. R. et al. Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease. Osteoarthritis Cartilage 17, 1040–1048 (2009).
  Article CAS PubMed Google Scholar
• Martel-Pelletier, J., Mineau, F., Jovanovic, D., Di Battista, J. A. & Pelletier, J. P. Mitogen-activated protein kinase and nuclear factor κB together regulate interleukin-17-induced nitric oxide production in human osteoarthritic chondrocytes: possible role of transactivating factor mitogen-activated protein kinase-activated proten kinase (MAPKAPK). Arthritis Rheum. 42, 2399–2409 (1999).
  Article CAS PubMed Google Scholar
• Lubberts, E., Joosten, L. A., van de Loo, F. A., van den Gersselaar, L. A. & van den Berg, W. B. Reduction of interleukin-17-induced inhibition of chondrocyte proteoglycan synthesis in intact murine articular cartilage by interleukin-4. Arthritis Rheum. 43, 1300–1306 (2000).
  Article CAS PubMed Google Scholar
• Olee, T., Hashimoto, S., Quach, J. & Lotz, M. IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses. J. Immunol. 162, 1096–1100 (1999).
  CAS PubMed Google Scholar
• Alaaeddine, N. et al. Differential effects of IL-8, LIF (pro-inflammatory) and IL-11 (anti-inflammatory) on TNF-α-induced PGE2 release and on signalling pathways in human OA synovial fibroblasts. Cytokine 11, 1020–1030 (1999).
  Article CAS PubMed Google Scholar
• Ishii, H. et al. Characterization of infiltrating T cells and TH1/TH2-type cytokines in the synovium of patients with osteoarthritis. Osteoarthritis Cartilage 10, 277–281 (2002).
  Article CAS PubMed Google Scholar
• Alsalameh, S. et al. Cellular immune response toward human articular chondrocytes. T cell reactivities against chondrocyte and fibroblast membranes in destructive joint diseases. Arthritis Rheum. 33, 1477–1486 (1990).
  Article CAS PubMed Google Scholar
• Pacquelet, S. et al. Interleukin 17, a nitric oxide-producing cytokine with a peroxynitrite-independent inhibitory effect on proteoglycan synthesis. J. Rheumatol. 29, 2602–2610 (2002).
  CAS PubMed Google Scholar
• Benderdour, M. et al. Interleukin 17 (IL-17) induces collagenase-3 production in human osteoarthritic chondrocytes via AP-1 dependent activation: differential activation of AP-1 members by IL-17 and IL-1β. J. Rheumatol. 29, 1262–1272 (2002).
  CAS PubMed Google Scholar
• Honorati, M. C., Bovara, M., Cattini, L., Piacentini, A. & Facchini, A. Contribution of interleukin 17 to human cartilage degradation and synovial inflammation in osteoarthritis. Osteoarthritis Cartilage 10, 799–807 (2002).
  Article CAS PubMed Google Scholar
• Kauffmann, C. et al. Computer-aided method for quantification of cartilage thickness and volume changes using MRI: validation study using a synthetic model. IEEE Trans. Biomed. Eng. 50, 978–988 (2003).
  Article PubMed Google Scholar
• Raynauld, J. P. et al. Reliability of a quantification imaging system using magnetic resonance images to measure cartilage thickness and volume in human normal and osteoarthritic knees. Osteoarthritis Cartilage 11, 351–360 (2003).
  Article PubMed Google Scholar
• Berthiaume, M. J. et al. Meniscal tear and extrusion are strongly associated with progression of symptomatic knee osteoarthritis as assessed by quantitative magnetic resonance imaging. Ann. Rheum. Dis. 64, 556–563 (2005).
  Article PubMed Google Scholar
• Raynauld, J. P. et al. Correlation between bone lesion changes and cartilage volume loss in patients with osteoarthritis of the knee as assessed by quantitative magnetic resonance imaging over a 24-month period. Ann. Rheum. Dis. 67, 683–688 (2008).
  Article PubMed Google Scholar
• Pelletier, J. P. et al. A new non-invasive method to assess synovitis severity in relation to symptoms and cartilage volume loss in knee osteoarthritis patients using MRI. Osteoarthritis Cartilage 16 (Suppl. 3), S8–S13 (2008).
  Article PubMed Google Scholar
• Li, W. et al. Human hip joint cartilage: MRI quantitative thickness and volume measurements discriminating acetabulum and femoral head. IEEE Trans. Biomed. Eng. 55, 2731–2740 (2008).
  Article PubMed Google Scholar
• Li, W. et al. Fully automated system for the quantification of human osteoarthritic knee joint effusion volume using magnetic resonance imaging. Arthritis Res. Ther. 12, R173 (2010).
  Article PubMed PubMed Central Google Scholar