Objective: To compare the levels of MMP-13 and TNF-ain late stage osteoarthritis, deŞne their predominant pathways and investigate their correlation with McMaster Universities Arthritis Index scores.Patients and methods: A total of 42 patients (mean age 64± 8.8) with grade 3 and grade 4 knee osteoarthritis according to Kellegren- Lawrence criteria and who were scheduled for total knee arthroplastywere enrolled in the study. TNF-alpha and MMP-13 levels were measured preoperatively from venousblood samples and intraoperatively from knee synovialﬂuid via ELISA. Preoperative and 1 monthpostoperative knee functions were assessed by McMaster Universities Arthritis Index.Results: Grade 4 synovialﬂuid MMP-13 (4.76 ± 5.82) was elevated compared to grade 3 (3.95 ± 4.45)(p¼ 0.438), whereas grade 3 serum MMP-13 (1.128 ± 0.308) was found elevated compared to grade 4(1.038± 0.204) (p ¼ 0.430). Grade 4 serum TNF-a(0.253± 0.277) was elevated compared to grade 3(0.206± 0.219) whereas grade 3 synovial ﬂuid TNF-a(0.129± 0.052) was elevated compared to grade 4(0.118± 0.014). Positive correlation was observed between synovial ﬂuid MMP-13 levels and postoperative WOMAC scores. Mean serum TNF-alevel (0.226± 0.246 pg/ml) was found higher compared tosynovial level (0.124± 1.59), synovial MMP-13 level (4.31 ± 1.24) was found higher compared to serumlevel (1.089± 1.519).Conclusion: Despite the systemic increase in TNF-alevels concordant with osteoarthritis grade, MMP-13levels are elevated via local manner with a signiŞcant correlation with WOMAC scores.Level of evidence: Level IV, Diagnostic study
1. Atik OS. Is subchondral bone the crucial point for the pathogenesis and the treatment of osteoarthritis? Eklem Hast Cerrahisi. 2014;25:1.
2. Martel-Pelletier J, Pelletier JP. Is osteoarthritis a disease involving only cartilage or other articular tissues? Eklem Hast Cerrahisi. 2010;21:2e14.
3. Cooper C, Snow S, McAlindon TE, et al. Risk factors for the incidence and progression of radiographic knee osteoarthritis. Arthritis Rheum. 2000;43: 995e1000.
4. Atik OS, Tokgoz N. Do periarticular dense bone islands cause cartilage destruction? Eklem Hast Cerrahisi. 2013;24:39e40.
5. Tashman S, Collon D, Anderson K, Kolowich P, Anderst W. Abnormal rotational knee motion during running after anterior cruciate ligament reconstruction. Am J Sports Med. 2004;32:975e983.
6. Nishimura A, Hasegawa M, Kato K, Yamada T, Uchida A, Sudo A. Risk factors for the incidence and progression of radiographic osteoarthritis of the knee among Japanese. Int Orthop. 2011;35:839e843.
7. Malemud CJ, Islam N, Haqqi TM. Pathophysiological mechanisms in osteoarthritis lead to novel therapeutic strategies. Cells Tissues Organs. 2003;174:34e48.
8. Miller RE, Miller RJ, Malfait AM. Osteoarthritis joint pain: the cytokine connection. Cytokine. 2014;70:185e193.
9. MacFarlane RJ, Graham SM, Davies PS, et al. Anti-inflammatory role and immunomodulation of mesenchymal stem cells in systemic joint diseases: potential for treatment. Expert Opin Ther Targets. 2013;17:243e254.
10. Santangelo KS, Nuovo GJ, Bertone AL. In vivo reduction or blockade of interleukin-1b in primary osteoarthritis influences expression of mediators implicated in pathogenesis. Osteoarthr Cartil. 2012;20:1610e1689.
11. Wang W, Kang W, Tang Q, et al. Cilostazol prevents the degradation of collagen Type II in human chondrocytes. Biochem Biophys Res Commun. 2014;451: 352e355.
12. Zhang X, Zhu Y, Chen X, et al. Baicalein ameliorates inflammatory-related apoptotic and catabolic phenotypes in human chondrocytes. Int Immunopharmacol. 2014;21:301e308.
13. Tang P, Hung M-C, Klostergaard J. Human pro-tumor necrosis factor is a homotrimer. Biochemistry. 1996;35:8216e8225.
14. Kriegler M, Perez C, DeFay K, Albert I, Lu SD. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell. 1998;53:45e53.
15. Olszewski MB, Groot AJ, Dastych J, Knol EF. TNF trafficking to human mast cell granules: mature chain-dependent endocytosis. J Immunol. 2007;178: 5701e5709.
16. Alaaeddine N, Hilal G, Baddoura R, Antoniou J, Di Battista JA. CCL20 stimulates proinflammatory mediator synthesis in human fibroblast-like synoviocytes through a MAP kinase-dependent process with transcriptional and posttranscriptional control. J Rheumatol. 2011;38:1858e1865.
17. Alaaeddine N, Di Battista JA, Pelletier JP, Kiansa K, Cloutier JM. Martel-Pelletier J.Differential effects of IL-8, LIF (pro-inflammatory) and IL-11 (anti-inflammatory) on TNF-alpha-induced PGE(2)release and on signalling pathways in human OA synovial fibroblasts. Cytokine. 1999;11:1020e1030.
18. Hermann J, Lipp RW, Dunzinger A, et al. Anti-TNF scintigraphy to assess TNF-aassociated joint inflammation in rheumatoid arthritis and osteoarthritis. Clin Exp Rheumatol. 2014;32(4):614.
19. Quintana JM, Escobar A, Arostegui I, et al. Health-related quality of life and appropriateness of knee or hip joint replacement. Archives Intern Med. 2006;166:220e226.
20. Loeuille D, Chary-Valckenaere I, Champigneulle J, Rat AC, Toussaint F, PinzanoWatrin A. Macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee: correlating magnetic resonance imaging findings with disease severity. Arthritis Rheum. 2005;52:3492e3501.
21. Wassilew GI, Lehnigk U, Duda GN, Taylor WR, Matziolis G, Dynybil C. The expression of proinflammatory cytokines and matrix metalloproteinases in the synovial membranes of patients with osteoarthritis compared with traumatic knee disorders. Arthroscopy. 2010;26:1096e1104.
22. Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE. 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. 2006;8:R187.
23. Haack M, Pollmacher T, Mullington JM. Diurnal and sleep-wake dependent variations of soluble TNF- and IL-2 receptors in healthy volunteers. Brain Behav Immun. 2004;18:361e367.
24. Payette C, Blackburn P, Lamarche B, et al. Sex differences in postprandial plasma tumor necrosis factor-alpha, interleukin-6, and C-reactive protein concentrations. Metabolism. 2009;58:1593e1601.
25. Zhou Xin. Conceptual and methodological issues relevant to cytokine and in- flammatory marker measurements in clinical research. Curr Opin Clin Nutr Metab Care. 2010 September;13(5):541e547.
26. Benito MJ, Veale DJ, FitzGerald O, Van den Berg WB, Bresnihan B. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis. 2005;64: 1263e1267.
27. Aktas E, Sener E, Gocun PU. Mechanically induced experimental knee osteoarthritis benefits from anti-inflammatory and immunomodulatory properties of simvastatin via inhibition of matrix metalloproteinase-3. Orthop Traumatol. 2011;12:145e151.
28. Yang Q, Wu S, Mao X, Wang W, Tai H. Inhibition effect of curcumin on TNFalpha and MMP-13 expression induced by advanced glycation end products in chondrocytes. Pharmacology. 2013;91:77e85.
29. Park SJ, Cheon EJ, Lee MH, Kim HA. MicroRNA-127-5p regulates matrix metalloproteinase 13 expression and interleukin-1beta-induced catabolic effects in human chondrocytes. Arthritis Rheum. 2013;65:3141e3152.
30. Kobayashi M, Squires GR, Mousa A, et al. Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage. Arthritis Rheum. 2005;52:128e135.
31. Ryu JH, Lee A, Na JH, et al. Optimization of matrix metalloproteinase fluorogenic probes for osteoarthritis imaging. Amino Acids. 2011;41:1113e1122.
32. Rutgers M, Saris DB, Dhert WJ, Creemers LB. Cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitro effects on cartilage metabolism and intra-articular levels after injection. Arthritis Res Ther. 2010;12:114.