Vol 78, No 3 (2019)
Original article
Published online: 2018-10-16

open access

Page views 1676
Article views/downloads 1384
Get Citation

Connect on Social Media

Connect on Social Media

Expression of matrix metalloproteinase-9 and tumour necrosis factor-alpha in the synovial cells of patients with meniscus tears

R. Atiç1, E. Deveci2
Pubmed: 30371936
Folia Morphol 2019;78(3):535-544.

Abstract

Background: A meniscus tear is a serious trauma that develops during swinging motion of the fixed foot. Meniscus tears may also be accompanied by divergence of the lateral ligaments of the knee joint.

Materials and methods: We enrolled 45 males and 35 females with meniscal tears in the present study. Patients with local joint pain, swelling, difficulty climbing stairs, patellar creeping, difficulties with daily living activities, local pain on palpation, and walking and running complaints, were included. We performed preoperative magnetic resonance imaging. Synovial fluid (5 mL) was aspirated from the lateral suprapatellar pouch of each knee with meniscal pain with the patient in the supine position. Blood samples were taken and biochemical parameters were analysed. The Harris haematoxylin and eosin staining protocol was used to evaluate tissue samples, and the levels of anti-matrix metalloproteinase (MMP)-9 and anti-tumour necrosis factor alpha (TNF-α) antibodies were measured immunohistochemically.

Results: Increased numbers of lymphocytes and neutrophils, hyperplastic erythrocytes, and fibroblasts were observed in the joint fluid of females. In males, the fibroblast cells were hyperplastic and plasma cell numbers were increased. MMP-9 expression was elevated in plasma cells, fibroblasts, and neutrophils; and TNF-α expression was observed in lymphocytes and polymorphic nucleated cells. We suggest that increased fluid levels in inflamed joints with meniscal tears, and the associated inflammation, disrupt the cartilage matrix and elevate the production of cytokines such as TNF-α and MMP-9 via release from cells such as fibroblasts that synthesise these mediators.

Conclusions: Anti-TNF-α treatment may prevent meniscal tears and prevent or slow the development of osteoarthritis.

Article available in PDF format

View PDF Download PDF file

References

  1. Aggarwal BB, Gupta SC, Sung B. Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. Br J Pharmacol. 2013; 169(8): 1672–1692.
  2. Balakrishnan L, Nirujogi RS, Ahmad S, et al. Proteomic analysis of human osteoarthritis synovial fluid. Clin Proteomics. 2014; 11(1): 6.
  3. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil. 2013; 21(1): 16–21.
  4. Bigoni M, Sacerdote P, Turati M, et al. Acute and late changes in intraarticular cytokine levels following anterior cruciate ligament injury. J Orthop Res. 2013; 31(2): 315–321.
  5. Brophy RH, Rai MF, Zhang Z, et al. Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear. J Bone Joint Surg Am. 2012; 94(5): 385–393.
  6. Brophy RH, Wojahn RD, Lillegraven O, et al. Outcomes of Arthroscopic Posterior Medial Meniscus Root Repair: Association With Body Mass Index. J Am Acad Orthop Surg. 2019; 27(3): 104–111.
  7. Buma P, Ramrattan NN, van Tienen TG, et al. Tissue engineering of the meniscus. Biomaterials. 2004; 25(9): 1523–1532.
  8. Cuellar VG, Cuellar JM, Golish SR, et al. Cytokine profiling in acute anterior cruciate ligament injury. Arthroscopy. 2010; 26(10): 1296–1301.
  9. Englund M, Roemer FW, Hayashi D, et al. The role of the meniscus in knee osteoarthritis: a cause or consequence? Radiol Clin North Am. 2009; 47(4): 703–712.
  10. Fox AJS, Bedi A, Rodeo SA. The basic science of human knee menisci: structure, composition, and function. Sports Health. 2012; 4(4): 340–351.
  11. Fox AJS, Wanivenhaus F, Burge AJ, et al. The human meniscus: a review of anatomy, function, injury, and advances in treatment. Clin Anat. 2015; 28(2): 269–287.
  12. Ghosh N, Kruse D, Subeh M, et al. Comparing Point-of-care-ultrasound (POCUS) to MRI for the Diagnosis of Medial Compartment Knee Injuries. J Med Ultrasound. 2017; 25(3): 167–172.
  13. Gray JC. Neural and vascular anatomy of the menisci of the human knee. J Orthop Sports Phys Ther. 1999; 29(1): 23–30.
  14. Haack M, Pollmächer T, Mullington JM. Diurnal and sleep-wake dependent variations of soluble TNF- and IL-2 receptors in healthy volunteers. Brain Behav Immun. 2004; 18(4): 361–367.
  15. Hart HF, Crossley KM, Felson D, et al. Relation of meniscus pathology to prevalence and worsening of patellofemoral joint osteoarthritis: the Multicenter Osteoarthritis Study. Osteoarthr Cartil. 2018; 26(7): 912–919.
  16. Hart HF, Crossley KM, Hunt MA. Gait patterns, symptoms, and function in patients with isolated tibiofemoral osteoarthritis and combined tibiofemoral and patellofemoral osteoarthritis. J Orthop Res. 2018; 36(6): 1666–1672.
  17. Hsieh YS, Yang SF, Chu SC, et al. Expression changes of gelatinases in human osteoarthritic knees and arthroscopic debridement. Arthroscopy. 2004; 20(5): 482–488.
  18. Irie K, Uchiyama E, Iwaso H. Intraarticular inflammatory cytokines in acute anterior cruciate ligament injured knee. Knee. 2003; 10(1): 93–96.
  19. Jones AO, Houang MTW, Low RS, et al. Medial meniscus posterior root attachment injury and degeneration: MRI findings. Australas Radiol. 2006; 50(4): 306–313.
  20. Koryem H, Wanas M, Rizk M, et al. Evaluation of early changes of cartilage biomarkers following arthroscopic meniscectomy in young Egyptian adults. Alexandria J Med. 2019; 51(3): 191–197.
  21. Lawrence JT, Birmingham J, Toth AP. Emerging ideas: prevention of posttraumatic arthritis through interleukin-1 and tumor necrosis factor-alpha inhibition. Clin Orthop Relat Res. 2011; 469(12): 3522–3526.
  22. Lewis JS, Hembree WC, Furman BD, et al. Acute joint pathology and synovial inflammation is associated with increased intra-articular fracture severity in the mouse knee. Osteoarthr Cartil. 2011; 19(7): 864–873.
  23. Lingen MW. Role of leukocytes and endothelial cells in the development of angiogenesis in inflammation and wound healing. Arch Pathol Lab Med. 2001; 125(1): 67–71.
  24. Liu B, Goode AP, Carter TE, et al. Matrix metalloproteinase activity and prostaglandin E2 are elevated in the synovial fluid of meniscus tear patients. Connect Tissue Res. 2017; 58(3-4): 305–316.
  25. Loeser RF. The effects of aging on the development of osteoarthritis. HSS J. 2012; 8(1): 18–19.
  26. Lohmander LS, Englund PM, Dahl LL, et al. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007; 35(10): 1756–1769.
  27. Lotz M, Martel-Pelletier J, Christiansen C, et al. Value of biomarkers in osteoarthritis: current status and perspectives. Ann Rheum Dis. 2013; 72(11): 1756–1763.
  28. Lotz MK, Kraus VB. New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options. Arthritis Res Ther. 2010; 12(3): 211.
  29. McNulty AL, Rothfusz NE, Leddy HA, et al. Synovial fluid concentrations and relative potency of interleukin-1 alpha and beta in cartilage and meniscus degradation. J Orthop Res. 2013; 31(7): 1039–1045.
  30. Mott JD, Werb Z. Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol. 2004; 16(5): 558–564.
  31. Nagase H, Woessner JF. Matrix metalloproteinases. J Biol Chem. 1999; 274(31): 21491–21494.
  32. Ogura T, Suzuki M, Sakuma Y, et al. Differences in levels of inflammatory mediators in meniscal and synovial tissue of patients with meniscal lesions. J Exp Orthop. 2016; 3(1): 7.
  33. Orita S, Koshi T, Mitsuka T, et al. Associations between proinflammatory cytokines in the synovial fluid and radiographic grading and pain-related scores in 47 consecutive patients with osteoarthritis of the knee. BMC Musculoskelet Disord. 2011; 12: 144.
  34. Overall CM. Molecular determinants of metalloproteinase substrate specificity: matrix metalloproteinase substrate binding domains, modules, and exosites. Mol Biotechnol. 2002; 22(1): 51–86.
  35. Ozkoc G, Circi E, Gonc U, et al. Radial tears in the root of the posterior horn of the medial meniscus. Knee Surg Sports Traumatol Arthrosc. 2008; 16(9): 849–854.
  36. Page-McCaw A, Ewald AJ, Werb Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol. 2007; 8(3): 221–233.
  37. Papalia R, Papalia G, Russo F, et al. Meniscal extrusion as booster of osteoarthritis. J Biol Regul Homeost Agents. 2017; 31(4 Suppl 2): 33–44.
  38. Papalia R, Vasta S, Franceschi F, et al. Meniscal root tears: from basic science to ultimate surgery. Br Med Bull. 2013; 106: 91–115.
  39. 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(11): 1593–1601.
  40. Peña E, Calvo B, Martínez MA, et al. Finite element analysis of the effect of meniscal tears and meniscectomies on human knee biomechanics. Clin Biomech. 2005; 20(5): 498–507.
  41. Penninx BW, Abbas H, Ambrosius W, et al. Inflammatory markers and physical function among older adults with knee osteoarthritis. J Rheumatol. 2004; 31(10): 2027–2031.
  42. Rutgers M, Saris DBF, Dhert WJA, et al. 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(3): R114.
  43. Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012; 51(2): 249–257.
  44. Sharon Tan SH, Kripesh A, Chan CX, et al. Gender differences in intra-articular and extra-articular injuries associated with acute anterior cruciate ligament ruptures. J Knee Surg. 2018 [Epub ahead of print].
  45. Stone AV, Loeser RF, Vanderman KS, et al. Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis. Osteoarthr Cartil. 2014; 22(2): 264–274.
  46. Swärd P, Frobell R, Englund M, et al. Cartilage and bone markers and inflammatory cytokines are increased in synovial fluid in the acute phase of knee injury (hemarthrosis)--a cross-sectional analysis. Osteoarthr Cartil. 2012; 20(11): 1302–1308.
  47. Tsai SH, Liang YC, Chen L, et al. Arsenite stimulates cyclooxygenase-2 expression through activating IkappaB kinase and nuclear factor kappaB in primary and ECV304 endothelial cells. J Cell Biochem. 2002; 84(4): 750–758.
  48. Zhou X, Fragala MS, McElhaney JE, et al. Conceptual and methodological issues relevant to cytokine and inflammatory marker measurements in clinical research. Curr Opin Clin Nutr Metab Care. 2010; 13(5): 541–547.