The Effects of Adipokines on Cartilage and Meniscus Catabolism

REFERENCES

• Kraus, V.B. (1997). Pathogenesis and treatment of osteoarthritis. Med. Clin. North Am. 81(1):85–112.
   PubMed Web of Science ®Google Scholar
• Poole, A.R., Guilak, F., and Abramson, S.B. (2007). Etiopathogenesis of osteoarthritis. In Osteoarthritis: Diagnosis and Medical/Surgical Management, 4th ed., R.W. Moskowitz, R. Altman, M. Hochberg, J. Buckwalter, and V.M. Goldberg ( eds.) pp. 27–49. Philadelphia, PA: Lippincott Williams and Wilkins.
   Google Scholar
• Hochberg, M.C. (1997). Osteoarthritis: Clinical features and treatment. In Primer on the Rheumatic Diseases, 11th ed., J.H. Klippel (ed.) pp. 218–221. Atlanta: Arthritis Foundation.
   Google Scholar
• Cicuttini, F.M., Baker, J.R., and Spector, T.D. (1996). The association of obesity with osteoarthritis of the hand and knee in women: A twin study. J. Rheumatol. 23(7):1221–1226.
   PubMed Web of Science ®Google Scholar
• Grotle, M., Hagen, K.B., Natvig, B., Dahl, F.A., and Kvien, T.K. (2008). Obesity and osteoarthritis in knee, hip and/or hand: An epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet. Disord. 9:132.
   PubMed Web of Science ®Google Scholar
• Ozkoc, G., Circi, E., Gonc, U., Irgit, K., Pourbagher, A., and Tandogan, R.N. (2008). Radial tears in the root of the posterior horn of the medial meniscus. Knee Surg. Sports Traumatol. Arthrosc. 16(9):849–854.
   PubMed Web of Science ®Google Scholar
• Wyland, D.J., Guilak, F., Elliott, D.M., Setton, L.A., and Vail, T.P. (2002). Chondropathy after meniscal tear or partial meniscectomy in a canine model. J. Orthop. Res. 20(5):996–1002.
   PubMed Web of Science ®Google Scholar
• Christoforakis, J., Pradhan, R., Sanchez-Ballester, J., Hunt, N., and Strachan, R.K. (2005). Is there an association between articular cartilage changes and degenerative meniscus tears? Arthroscopy 21(11):1366–1369.
   PubMed Web of Science ®Google Scholar
• Roos, H., Lauren, M., Adalberth, T., Roos, E.M., Jonsson, K., and Lohmander, L.S. (1998). Knee osteoarthritis after meniscectomy: Prevalence of radiographic changes after twenty-one years, compared with matched controls. Arthritis Rheum. 41(4):687–693.
   PubMed Web of Science ®Google Scholar
• Hunter, D.J., Zhang, Y.Q., Niu, J.B., Tu, X., Amin, S., Clancy, M., Guermazi, A., Grigorian, M., Gale, D., and Felson, D.T. (2006). The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis. Arthritis Rheum. 54(3):795–801.
   PubMed Web of Science ®Google Scholar
• Burger, C., Kabir, K., Mueller, M., Rangger, C., Minor, T., and Tolba, R.H. (2006). Retropatellar chondromalacia associated with medial osteoarthritis after meniscus injury. One year of observations in sheep. Eur. Surg. Res. 38(2):102–108.
   PubMed Web of Science ®Google Scholar
• Lindhorst, E., Vail, T.P., Guilak, F., Wang, H., Setton, L.A., Vilim, V., and Kraus, V.B. (2000). Longitudinal characterization of synovial fluid biomarkers in the canine meniscectomy model of osteoarthritis. J. Orthop. Res. 18(2):269–280.
   PubMed Web of Science ®Google Scholar
• Galic, S., Oakhill, J.S., and Steinberg, G.R. (2010). Adipose tissue as an endocrine organ. Mol. Cell. Endocrinol. 316(2):129–139.
   PubMed Web of Science ®Google Scholar
• Otero, M., Lago, R., Gomez, R., Lago, F., Dieguez, C., Gomez-Reino, J.J., and Gualillo, O. (2006). Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann. Rheum. Dis. 65(9):1198–1201.
   PubMed Web of Science ®Google Scholar
• Ding, C., Parameswaran, V., Cicuttini, F., Burgess, J., Zhai, G., Quinn, S., and Jones, G. (2008). Association between leptin, body composition, sex and knee cartilage morphology in older adults: The Tasmanian older adult cohort (TASOAC) study. Ann. Rheum. Dis. 67(9):1256–1261.
   PubMed Web of Science ®Google Scholar
• Ku, J.H., Lee, C.K., Joo, B.S., An, B.M., Choi, S.H., Wang, T.H., and Cho, H.L. (2009). Correlation of synovial fluid leptin concentrations with the severity of osteoarthritis. Clin. Rheumatol. 28(12):1431–1435.
   PubMed Web of Science ®Google Scholar
• Dumond, H., Presle, N., Terlain, B., Mainard, D., Loeuille, D., Netter, P., and Pottie, P. (2003). Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 48(11):3118–3129.
   PubMed Web of Science ®Google Scholar
• Simopoulou, T., Malizos, K.N., Iliopoulos, D., Stefanou, N., Papatheodorou, L., Ioannou, M., and Tsezou, A. (2007). Differential expression of leptin and leptin’s receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism. Osteoarthr. Cartil. 15(8):872–883.
   PubMed Web of Science ®Google Scholar
• Griffin, T.M., Fermor, B., Huebner, J.L., Kraus, V.B., Rodriguiz, R.M., Wetsel, W.C., Cao, L., Setton, L.A., and Guilak, F. (2010). Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice. Arthritis Res. Ther. 12(4):R130.
   PubMed Web of Science ®Google Scholar
• Griffin, T.M., Huebner, J.L., Kraus, V.B., and Guilak, F. (2009). Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheum. 60(10):2935–2944.
   PubMed Web of Science ®Google Scholar
• Fernandes, J.C., Martel-Pelletier, J., and Pelletier, J.P. (2002). The role of cytokines in osteoarthritis pathophysiology. Biorheology 39(1–2):237–246.
   PubMed Web of Science ®Google Scholar
• Lotz, M. (2001). Cytokines in cartilage injury and repair. Clin. Orthop. Relat. Res. 391(391 Suppl):S108–S115.
   PubMedGoogle Scholar
• Hopkins, S.J., Humphreys, M., and Jayson, M.I. (1988). Cytokines in synovial fluid. I. The presence of biologically active and immunoreactive IL-1. Clin. Exp. Immunol. 72(3):422–427.
   PubMed Web of Science ®Google Scholar
• Kahle, P., Saal, J.G., Schaudt, K., Zacher, J., Fritz, P., and Pawelec, G. (1992). Determination of cytokines in synovial fluids: Correlation with diagnosis and histomorphological characteristics of synovial tissue. Ann. Rheum. Dis. 51(6):731–734.
   PubMed Web of Science ®Google Scholar
• Lotz, M., Blanco, F.J., von Kempis, J., Dudler, J., Maier, R., Villiger, P.M., and Geng, Y. (1995). Cytokine regulation of chondrocyte functions. J. Rheumatol. Suppl. 43:104–108.
   PubMedGoogle Scholar
• van den Berg, W.B., Joosten, L.A., and van de Loo, F.A. (1999). TNF alpha and IL-1 beta are separate targets in chronic arthritis. Clin. Exp. Rheumatol 17(6 Suppl 18):S105–S114.
   PubMed Web of Science ®Google Scholar
• Hubbard, J.R., Steinberg, J.J., Bednar, M.S., and Sledge, C.B. (1988). Effect of purified human interleukin-1 on cartilage degradation. J. Orthop. Res. 6(2):180–187.
   PubMed Web of Science ®Google Scholar
• Pelletier, J.P., DiBattista, J.A., Roughley, P., McCollum, R., and Martel-Pelletier, J. (1993). Cytokines and inflammation in cartilage degradation. Rheum. Dis. Clin. North Am. 19(3):545–568.
   PubMed Web of Science ®Google Scholar
• Stefanovic-Racic, M., Mollers, M.O., Miller, L.A., and Evans, C.H. (1997). Nitric oxide and proteoglycan turnover in rabbit articular cartilage. J. Orthop. Res. 15(3):442–449.
   PubMed Web of Science ®Google Scholar
• Cao, M., Stefanovic-Racic, M., Georgescu, H.I., Miller, L.A., and Evans, C.H. (1998). Generation of nitric oxide by lapine meniscal cells and its effect on matrix metabolism: Stimulation of collagen production by arginine. J. Orthop. Res. 16(1):104–111.
   PubMed Web of Science ®Google Scholar
• Shin, S.J., Fermor, B., Weinberg, J.B., Pisetsky, D.S., and Guilak, F. (2003). Regulation of matrix turnover in meniscal explants: Role of mechanical stress, interleukin-1, and nitric oxide. J. Appl. Physiol. 95(1):308–313.
   PubMed Web of Science ®Google Scholar
• Sanchez, C., Deberg, M.A., Burton, S., Devel, P., Reginster, J.Y., and Henrotin, Y.E. (2004). Differential regulation of chondrocyte metabolism by oncostatin M and interleukin-6. Osteoarthr. Cartil. 12(10):801–810.
   PubMed Web of Science ®Google Scholar
• Guerne, P.A., Carson, D.A., and Lotz, M. (1990). IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J. Immunol. 144(2):499–505.
   PubMed Web of Science ®Google Scholar
• Livshits, G., Zhai, G., Hart, D.J., Kato, B.S., Wang, H., Williams, F.M., and Spector, T.D. (2009). Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: The Chingford Study. Arthritis Rheum. 60(7):2037–2045.
   PubMed Web of Science ®Google Scholar
• Fonseca, J.E., Santos, M.J., Canhao, H., and Choy, E. (2009). Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun. Rev. 8(7):538–542.
   PubMed Web of Science ®Google Scholar
• Rowan, A.D., Koshy, P.J., Shingleton, W.D., Degnan, B.A., Heath, J.K., Vernallis, A.B., Spaull, J.R., Life, P.F., Hudson, K., and Cawston, T.E. (2001). Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum. 44(7):1620–1632.
   PubMed Web of Science ®Google Scholar
• Desgeorges, A., Gabay, C., Silacci, P., Novick, D., Roux-Lombard, P., Grau, G., Dayer, J.M., Vischer, T., and Guerne, P.A. (1997). Concentrations and origins of soluble interleukin 6 receptor-alpha in serum and synovial fluid. J. Rheumatol. 24(8):1510–1516.
   PubMed Web of Science ®Google Scholar
• Distel, E., Cadoudal, T., Durant, S., Poignard, A., Chevalier, X., and Benelli, C. (2009). The infrapatellar fat pad in knee osteoarthritis: An important source of interleukin-6 and its soluble receptor. Arthritis Rheum. 60(11):3374–3377.
   PubMed Web of Science ®Google Scholar
• Loeser, R.F. (2003). Systemic and local regulation of articular cartilage metabolism: Where does leptin fit in the puzzle? Arthritis Rheum. 48(11):3009–3012.
   PubMed Web of Science ®Google Scholar
• Vuolteenaho, K., Koskinen, A., Kukkonen, M., Nieminen, R., Paivarinta, U., Moilanen, T., and Moilanen, E. (2009). Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage – Mediator role of NO in leptin-induced PGE2, IL-6, and IL-8 production. Mediators Inflamm. 2009:345838.
   PubMed Web of Science ®Google Scholar
• Otero, M., Lago, R., Gomez, R., Dieguez, C., Lago, F., Gomez-Reino, J., and Gualillo, O. (2006). Towards a pro-inflammatory and immunomodulatory emerging role of leptin. Rheumatology (Oxford) 45(8):944–950.
   PubMed Web of Science ®Google Scholar
• Silacci, P., Dayer, J.M., Desgeorges, A., Peter, R., Manueddu, C., and Guerne, P.A. (1998). Interleukin (IL)-6 and its soluble receptor induce TIMP-1 expression in synoviocytes and chondrocytes, and block IL-1-induced collagenolytic activity. J. Biol. Chem. 273(22):13625–13629.
   PubMed Web of Science ®Google Scholar
• Flannery, C.R., Little, C.B., Hughes, C.E., Curtis, C.L., Caterson, B., and Jones, S.A. (2000). IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage. Matrix Biol. 19(6):549–553.
   PubMed Web of Science ®Google Scholar
• Nowell, M.A., Richards, P.J., Fielding, C.A., Ognjanovic, S., Topley, N., Williams, A.S., Bryant-Greenwood, G., and Jones, S.A. (2006). Regulation of pre-B cell colony-enhancing factor by STAT-3-dependent interleukin-6 trans-signaling: Implications in the pathogenesis of rheumatoid arthritis. Arthritis Rheum. 54(7):2084–2095.
   PubMed Web of Science ®Google Scholar
• Bao, J.P., Chen, W.P., and Wu, L.D. (2009). Visfatin: A potential therapeutic target for rheumatoid arthritis. J. Int. Med. Res. 37(6):1655–1661.
   PubMed Web of Science ®Google Scholar
• Rho, Y.H., Solus, J., Sokka, T., Oeser, A., Chung, C.P., Gebretsadik, T., Shintani, A., Pincus, T., and Stein, C.M. (2009). Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis. Arthritis Rheum. 60(7):1906–1914.
   PubMed Web of Science ®Google Scholar
• Brentano, F., Schorr, O., Ospelt, C., Stanczyk, J., Gay, R.E., Gay, S., and Kyburz, D. (2007). Pre-B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix-degrading activities. Arthritis Rheum. 56(9):2829–2839.
   PubMed Web of Science ®Google Scholar
• Klein-Wieringa, I.R., Kloppenburg, M., Bastiaansen-Jenniskens, Y.M., Yusuf, E., Kwekkeboom, J.C., El-Bannoudi, H., Nelissen, R.G., Zuurmond, A., Stojanovic-Susulic, V., Van Osch, G.J., Toes, R.E., and Ioan-Facsinay, A. (2011). The infrapatellar fat pad of patients with osteoarthritis has an inflammatory phenotype. Ann. Rheum. Dis. 70(5):851–587.
   Google Scholar
• Gosset, M., Berenbaum, F., Salvat, C., Sautet, A., Pigenet, A., Tahiri, K., and Jacques, C. (2008). Crucial role of visfatin/pre-B cell colony-enhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: Possible influence on osteoarthritis. Arthritis Rheum. 58(5):1399–1409.
   PubMed Web of Science ®Google Scholar
• Presle, N., Pottie, P., Dumond, H., Guillaume, C., Lapicque, F., Pallu, S., Mainard, D., Netter, P., and Terlain, B. (2006). Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production. Osteoarthr. Cartil. 14(7):690–695.
   PubMed Web of Science ®Google Scholar
• Ushiyama, T., Chano, T., Inoue, K., and Matsusue, Y. (2003). Cytokine production in the infrapatellar fat pad: Another source of cytokines in knee synovial fluids. Ann. Rheum. Dis. 62(2):108–112.
   PubMed Web of Science ®Google Scholar
• Irie, K., Uchiyama, E., and Iwaso, H. (2003). Intraarticular inflammatory cytokines in acute anterior cruciate ligament injured knee. Knee 10(1):93–96.
   PubMed Web of Science ®Google Scholar
• Higuchi, H., Shirakura, K., Kimura, M., Terauchi, M., Shinozaki, T., Watanabe, H., and Takagishi, K. (2006). Changes in biochemical parameters after anterior cruciate ligament injury. Int. Orthop. 30(1):43–47.
   PubMed Web of Science ®Google Scholar
• Kotake, S., Sato, K., Kim, K.J., Takahashi, N., Udagawa, N., Nakamura, I., Yamaguchi, A., Kishimoto, T., Suda, T., and Kashiwazaki, S. (1996). Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation. J. Bone Miner. Res. 11(1):88–95.
   PubMed Web of Science ®Google Scholar
• Deng, S.-J., Bickett, D.M., Mitchell, J.L., Lambert, M.H., Blackburn, R.K., Carter III, H.L.C., Neugebauer, J., Pahel, G., Weiner, M.P., and Moss, M.L. (2000). Substrate specificity of human collagenase 3 assessed using a phage-displayed peptide library. J. Biol. Chem. 275:31422–31427.
   PubMed Web of Science ®Google Scholar
• McNulty, A.L., Estes, B.T., Wilusz, R.E., Weinberg, J.B., and Guilak, F. (2010). Dynamic loading enhances integrative meniscal repair in the presence of interleukin-1. Osteoarthr. Cartil. 18(6):830–838.
   PubMed Web of Science ®Google Scholar
• McNulty, A.L., Weinberg, J.B., and Guilak, F. (2009). Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus. Clin. Orthop. Relat. Res. 467(6):1557–1567.
   PubMed Web of Science ®Google Scholar
• Wilusz, R.E., Weinberg, J.B., Guilak, F., and McNulty, A.L. (2008). Inhibition of integrative repair of the meniscus following acute exposure to interleukin-1 in vitro. J. Orthop. Res. 26:504–512.
   PubMed Web of Science ®Google Scholar
• Farndale, R.W., Buttle, D.J., and Barrett, A.J. (1986). Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim. Biophys. Acta 883(2):173–177.
   PubMed Web of Science ®Google Scholar
• Granger, D.L., Anstey, N.M., Miller, W.C., and Weinberg, J.B. (1999). Measuring nitric oxide production in human clinical studies. Methods Enzymol. 301:49–61.
   PubMed Web of Science ®Google Scholar
• Fermor, B., Weinberg, J.B., Pisetsky, D.S., Misukonis, M.A., Fink, C., and Guilak, F. (2002). Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway. Osteoarthr. Cartil. 10(10):792–798.
   PubMed Web of Science ®Google Scholar
• Honsawek, S., and Chayanupatkul, M. (2010). Correlation of plasma and synovial fluid adiponectin with knee osteoarthritis severity. Arch. Med. Res. 41(8):593–598.
   PubMed Web of Science ®Google Scholar
• Schaffler, A., Ehling, A., Neumann, E., Herfarth, H., Tarner, I., Scholmerich, J., Muller-Ladner, U., and Gay, S. (2003). Adipocytokines in synovial fluid. JAMA 290(13):1709–1710.
   PubMed Web of Science ®Google Scholar
• Senolt, L., Housa, D., Vernerova, Z., Jirasek, T., Svobodova, R., Veigl, D., Anderlova, K., Muller-Ladner, U., Pavelka, K., and Haluzik, M. (2007). Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum. Ann. Rheum. Dis. 66(4):458–463.
   PubMed Web of Science ®Google Scholar
• Bokarewa, M., Nagaev, I., Dahlberg, L., Smith, U., and Resistin, T.A. (2005). An adipokine with potent proinflammatory properties. J. Immunol. 174(9):5789–5795.
   PubMed Web of Science ®Google Scholar
• Steppan, C.M., Crawford, D.T., Chidsey-Frink, K.L., Ke, H., and Swick, A.G. (2000). Leptin is a potent stimulator of bone growth in ob/ob mice. Regul. Pept. 92(1–3):73–78.
   PubMed Web of Science ®Google Scholar
• Koskinen, A., Vuolteenaho, K., Nieminen, R., Moilanen, T., and Moilanen, E. (2011). Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients. Clin. Exp. Rheumatol. 29(1):57–64.
   PubMed Web of Science ®Google Scholar
• Otero, M., Lago, R., Lago, F., Reino, J.J., and Gualillo, O. (2005). Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: Synergistic effect of leptin with interleukin-1. Arthritis Res. Ther. 7(3):R581–R591.
   PubMed Web of Science ®Google Scholar
• Bao, J.P., Chen, W.P., Feng, J., Hu, P.F., Shi, Z.L., and Wu, L.D. (2010). Leptin plays a catabolic role on articular cartilage. Mol. Biol. Rep. 37(7):3265–3272.
   PubMed Web of Science ®Google Scholar
• Pallu, S., Francin, P.J., Guillaume, C., Gegout-Pottie, P., Netter, P., Mainard, D., Terlain, B., and Presle, N. (2010). Obesity affects the chondrocyte responsiveness to leptin in patients with osteoarthritis. Arthritis Res. Ther. 12(3):R112.
   Web of Science ®Google Scholar
• Stannus, O., Jones, G., Cicuttini, F., Parameswaran, V., Quinn, S., Burgess, J., and Ding, C. (2010). Circulating levels of IL-6 and TNF-alpha are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults. Osteoarthr. Cartil. 18(11):1441–1447.
   PubMed Web of Science ®Google Scholar
• Gandhi, R., Takahashi, M., Smith, H., Rizek, R., and Mahomed, N.N. (2010). The synovial fluid adiponectin-leptin ratio predicts pain with knee osteoarthritis. Clin. Rheumatol. 29(11):1223–1228.
   PubMed Web of Science ®Google Scholar
• Griffin, T.M., and Guilak, F. (2008). Why is obesity associated with osteoarthritis? Insights from mouse models of obesity. Biorheology 45(3–4):387–398.
   PubMed Web of Science ®Google Scholar
• Elefteriou, F., Takeda, S., Ebihara, K., Magre, J., Patano, N., Kim, C.A., Ogawa, Y., Liu, X., Ware, S.M., Craigen, W.J., Robert, J.J., Vinson, C., Nakao, K., Capeau, J., and Karsenty, G. (2004). Serum leptin level is a regulator of bone mass. Proc. Natl. Acad. Sci. U.S. A. 101(9):3258–3263.
   PubMed Web of Science ®Google Scholar
• Lotz, M., and Guerne, P.A. (1991). Interleukin-6 induces the synthesis of tissue inhibitor of metalloproteinases-1/erythroid potentiating activity (TIMP-1/EPA). J. Biol. Chem. 266(4):2017–2020.
   PubMed Web of Science ®Google Scholar
• Sui, Y., Lee, J.H., DiMicco, M.A., Vanderploeg, E.J., Blake, S.M., Hung, H.H., Plaas, A.H., James, I.E., Song, X.Y., Lark, M.W., and Grodzinsky, A.J. (2009). Mechanical injury potentiates proteoglycan catabolism induced by interleukin-6 with soluble interleukin-6 receptor and tumor necrosis factor alpha in immature bovine and adult human articular cartilage. Arthritis Rheum. 60(10):2985–2996.
   PubMed Web of Science ®Google Scholar
• Legendre, F., Bogdanowicz, P., Boumediene, K., and Pujol, J.P. (2005). Role of interleukin 6 (IL-6)/IL-6R-induced signal tranducers and activators of transcription and mitogen-activated protein kinase/extracellular. J. Rheumatol. 32(7):1307–1316.
   PubMed Web of Science ®Google Scholar
• Milner, J.M., Elliott, S.-F., and Cawston, T.E. (2001). Activation of procollagenases is a key control point in cartilage collagen degradation: Interaction of serine and metalloproteinase pathways. Arthritis Rheum. 44(9):2084–2096.
   PubMed Web of Science ®Google Scholar
• Kimizuka, K., Nakao, A., Nalesnik, M.A., Demetris, A.J., Uchiyama, T., Ruppert, K., Fink, M.P., Stolz, D.B., and Murase, N. (2004). Exogenous IL-6 inhibits acute inflammatory responses and prevents ischemia/reperfusion injury after intestinal transplantation. Am. J. Transplant. 4(4):482–494.
   PubMed Web of Science ®Google Scholar
• Steensberg, A., Fischer, C.P., Keller, C., Moller, K., and Pedersen, B.K. (2003). IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am. J. Physiol. Endocrinol. Metab. 285(2):E433–E437.
   PubMed Web of Science ®Google Scholar
• Tilg, H., Trehu, E., Atkins, M.B., Dinarello, C.A., and Mier, J.W. (1994). Interleukin-6 (IL-6) as an anti-inflammatory cytokine: Induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood 83(1):113–118.
   PubMed Web of Science ®Google Scholar
• de Hooge, A.S., van de Loo, F.A., Bennink, M.B., Arntz, O.J., de Hooge, P., and van den Berg, W.B. (2005). Male IL-6 gene knock out mice developed more advanced osteoarthritis upon aging. Osteoarthr. Cartil. 13(1):66–73.
   PubMed Web of Science ®Google Scholar
• Van de Loo, F.A., Arntz, O.J., and Van den Berg, W.B. (1997). Effect of interleukin 1 and leukaemia inhibitory factor on chondrocyte metabolism in articular cartilage from normal and interleukin-6-deficient mice: Role of nitric oxide and IL-6 in the suppression of proteoglycan synthesis. Cytokine 9(7):453–462.
   PubMed Web of Science ®Google Scholar
• Busso, N., Karababa, M., Nobile, M., Rolaz, A., Van Gool, F., Galli, M., Leo, O., So, A., and De Smedt, T. (2008). Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD. PLoS One 3(5):e2267.
   PubMed Web of Science ®Google Scholar
• Duan, Y., Hao, D., Li, M., Wu, Z., Li, D., Yang, X., and Qiu, G. (2011). Increased synovial fluid visfatin is positively linked to cartilage degradation biomarkers in osteoarthritis. Rheumatol. Int. (in press).
   Google Scholar