Download PDF
J Knee Surg 2018; 31(09): 834-840
DOI: 10.1055/s-0037-1615821
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Metabolic Responses of Meniscus to IL-1β

Alex E. Cook
1   School of Medicine, Kansas City University of Medicine and Biosciences, Kansas City, Missouri
2   Department of Orthopaedic Surgery, Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
,
James L. Cook
2   Department of Orthopaedic Surgery, Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
3   Department of Orthopaedic Surgery, University of Missouri Health Care, Columbia, Missouri
,
Aaron M. Stoker
2   Department of Orthopaedic Surgery, Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
› Author Affiliations
Further Information

Publication History

11 October 2017

22 November 2017

Publication Date:
02 January 2018 (online)

    Permissions and Reprints

Abstract

This article identifies the potential mechanisms of action for meniscal degeneration in response to joint inflammation and potential contributions of the meniscus to the development and progression of osteoarthritis (OA). It was hypothesized that interleukin-1β (IL-1β) stimulation of meniscal explants would result in significant increases in nitric oxide (NO), matrix metalloproteinase (MMP) production and activity, and relevant cytokine production compared with controls. Canine meniscal explants (4 mm) were cultured for 21 days with (IL-1) or without (negative control [NC]) 50 ng/mL rcIL-1β (n = 6/group). Media were changed every 3 days and analyzed for MMP activity, ADAMTS-4 activity, MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, NO, prostaglandin E2 (PGE2), IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1), and keratinocyte-derived chemokine (KC) concentrations. Media NO and PGE2 concentrations were significantly higher in the IL-1 group at all time points except for days 9 and 12. The concentrations of MMP-13 were significantly higher in the IL-1 group at days 3, 6, 9, and 12. The production of MMP-2 was significantly lower in the IL-1 group on days 3 through 15. ADAMTS4 activity was significantly higher in the IL-1 group on days 6 through 18. MMP-3 concentrations and general MMP activity were significantly higher in the IL-1 group at all time points. Concentrations of IL-6, IL-8, MCP-1, and KC were significantly higher in the IL-1 group at most time points. Glycosaminoglycans (GAG) content decreased significantly (p = 0.009) in the IL-1 group compared with the NC group. Proinflammatory mediators appear to directly influence degradative processes in the meniscus, which in turn contribute to development and progression of OA by production of proinflammatory and degradative mediators. These findings have important clinical implications for the management of the degenerative meniscus and the osteoarthritic knee.

Keywords

meniscus - inflammation - ex vivo - meniscal degeneration - osteoarthritis
 

  • References

  • 1 Lawrence RC, Helmick CG, Arnett FC. , et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998; 41 (05) 778-799
    CrossrefPubMedSearch in Google Scholar
  • 2 Samuels J, Krasnokutsky S, Abramson SB. Osteoarthritis: a tale of three tissues. Bull NYU Hosp Jt Dis 2008; 66 (03) 244-250
    PubMedSearch in Google Scholar
  • 3 Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 2012; 64 (06) 1697-1707
    CrossrefPubMedSearch in Google Scholar
  • 4 Crema MD, Guermazi A, Li L. , et al. The association of prevalent medial meniscal pathology with cartilage loss in the medial tibiofemoral compartment over a 2-year period. Osteoarthritis Cartilage 2010; 18 (03) 336-343
    CrossrefPubMedSearch in Google Scholar
  • 5 Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med 2007; 35 (10) 1756-1769
    CrossrefPubMedSearch in Google Scholar
  • 6 Berthiaume M-J, Raynauld J-P, Martel-Pelletier 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 2005; 64 (04) 556-563
    CrossrefPubMedSearch in Google Scholar
  • 7 Hunter DJ, Zhang YQ, Niu JB. , et al. The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis. Arthritis Rheum 2006; 54 (03) 795-801
    CrossrefPubMedSearch in Google Scholar
  • 8 Lo GH, Hunter DJ, Nevitt M, Lynch J, McAlindon TE. ; OAI Investigators Group. Strong association of MRI meniscal derangement and bone marrow lesions in knee osteoarthritis: data from the osteoarthritis initiative. Osteoarthritis Cartilage 2009; 17 (06) 743-747
    CrossrefPubMedSearch in Google Scholar
  • 9 Jones JC, Burks R, Owens BD, Sturdivant RX, Svoboda SJ, Cameron KL. Incidence and risk factors associated with meniscal injuries among active-duty US military service members. J Athl Train 2012; 47 (01) 67-73
    CrossrefPubMedSearch in Google Scholar
  • 10 Messner K, Gao J. The menisci of the knee joint. Anatomical and functional characteristics, and a rationale for clinical treatment. J Anat 1998; 193 (Pt 2): 161-178
    CrossrefPubMedSearch in Google Scholar
  • 11 Goldring MB, Otero M, Plumb DA. , et al. Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur Cell Mater 2011; 21: 202-220
    CrossrefPubMedSearch in Google Scholar
  • 12 Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases. Arthritis Res Ther 2009; 11 (03) 224
    CrossrefPubMedSearch in Google Scholar
  • 13 Cook JL, Kuroki K, Stoker AM, Monibi FA, Roller BL. Meniscal biology in health and disease. Connect Tissue Res 2017; 58 (3-4): 225-237
    CrossrefPubMedSearch in Google Scholar
  • 14 Rai MF, McNulty AL. Meniscus beyond mechanics: using biology to advance our understanding of meniscus injury and treatment. Connect Tissue Res 2017; 58 (3-4): 221-224
    CrossrefPubMedSearch in Google Scholar
  • 15 Melrose J, Fuller ES, Little CB. The biology of meniscal pathology in osteoarthritis and its contribution to joint disease: beyond simple mechanics. Connect Tissue Res 2017; 58 (3-4): 282-294
    CrossrefPubMedSearch in Google Scholar
  • 16 Fox AJ, Wanivenhaus F, Burge AJ, Warren RF, Rodeo SA. The human meniscus: a review of anatomy, function, injury, and advances in treatment. Clin Anat 2015; 28 (02) 269-287
    CrossrefPubMedSearch in Google Scholar
  • 17 Farndale RW, Buttle DJ, Barrett AJ. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 1986; 883 (02) 173-177
    CrossrefPubMedSearch in Google Scholar
  • 18 Woodmass JM, LaPrade RF, Sgaglione NA, Nakamura N, Krych AJ. Meniscal repair: reconsidering indications, techniques, and biologic augmentation. J Bone Joint Surg Am 2017; 99 (14) 1222-1231
    CrossrefPubMedSearch in Google Scholar
  • 19 Abrams GD, Frank RM, Gupta AK, Harris JD, McCormick FM, Cole BJ. Trends in meniscus repair and meniscectomy in the United States, 2005-2011. Am J Sports Med 2013; 41 (10) 2333-2339
    CrossrefPubMedSearch in Google Scholar
  • 20 LeGrand A, Fermor B, Fink C. , et al. Interleukin-1, tumor necrosis factor α, and interleukin-17 synergistically up-regulate nitric oxide and prostaglandin E2 production in explants of human osteoarthritic knee menisci. Arthritis Rheum 2001; 44 (09) 2078-2083
    CrossrefPubMedSearch in Google Scholar
  • 21 Hashimoto S, Takahashi K, Ochs RL, Coutts RD, Amiel D, Lotz M. Nitric oxide production and apoptosis in cells of the meniscus during experimental osteoarthritis. Arthritis Rheum 1999; 42 (10) 2123-2131
    CrossrefPubMedSearch in Google Scholar
  • 22 Jang D, Murrell GAC. Nitric oxide in arthritis. Free Radic Biol Med 1998; 24 (09) 1511-1519
    CrossrefPubMedSearch in Google Scholar
  • 23 Hughes FJ, Buttery LDK, Hukkanen MVJ, O'Donnell A, Maclouf J, Polak JM. Cytokine-induced prostaglandin E2 synthesis and cyclooxygenase-2 activity are regulated both by a nitric oxide-dependent and -independent mechanism in rat osteoblasts in vitro. J Biol Chem 1999; 274 (03) 1776-1782
    CrossrefPubMedSearch in Google Scholar
  • 24 Guerne PA, Carson DA, Lotz M. IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J Immunol 1990; 144 (02) 499-505
    PubMedSearch in Google Scholar
  • 25 Lotz M, Terkeltaub R, Villiger PM. Cartilage and joint inflammation. Regulation of IL-8 expression by human articular chondrocytes. J Immunol 1992; 148 (02) 466-473
    PubMedSearch in Google Scholar
  • 26 Villiger PM, 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 1992; 90 (02) 488-496
    CrossrefPubMedSearch in Google Scholar
  • 27 Steensberg A, Fischer CP, Keller C, Møller K, Pedersen BK. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab 2003; 285 (02) E433-E437
    CrossrefPubMedSearch in Google Scholar
  • 28 Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood 1994; 83 (01) 113-118
    CrossrefPubMedSearch in Google Scholar
  • 29 Hammond MEW, Lapointe GR, Feucht PH. , et al. IL-8 induces neutrophil chemotaxis predominantly via type I IL-8 receptors. J Immunol 1995; 155 (03) 1428-1433
    PubMedSearch in Google Scholar
  • 30 Baggiolini M, Clark-Lewis I. Interleukin-8, a chemotactic and inflammatory cytokine. FEBS Lett 1992; 307 (01) 97-101
    CrossrefPubMedSearch in Google Scholar
  • 31 Chintakuntlawar AV, Chodosh J. Chemokine CXCL1/KC and its receptor CXCR2 are responsible for neutrophil chemotaxis in adenoviral keratitis. J Interferon Cytokine Res 2009; 29 (10) 657-666
    CrossrefPubMedSearch in Google Scholar
  • 32 Metzner B, Barbisch M, Parlow F, Kownatzki E, Schraufstatter I, Norgauer J. Interleukin-8 and GRO α prime human neutrophils for superoxide anion production and induce up-regulation of N-formyl peptide receptors. J Invest Dermatol 1995; 104 (05) 789-791
    CrossrefPubMedSearch in Google Scholar
  • 33 Taub DD, Proost P, Murphy WJ. , et al. Monocyte chemotactic protein-1 (MCP-1), -2, and -3 are chemotactic for human T lymphocytes. J Clin Invest 1995; 95 (03) 1370-1376
    CrossrefPubMedSearch in Google Scholar
  • 34 Matsushima K, Baldwin ET, Mukaida N. Interleukin-8 and MCAF: novel leukocyte recruitment and activating cytokines. Chem Immunol 1992; 51: 236-265
    PubMedSearch in Google Scholar
  • 35 Golds EE, Mason P, Nyirkos P. Inflammatory cytokines induce synthesis and secretion of gro protein and a neutrophil chemotactic factor but not β 2-microglobulin in human synovial cells and fibroblasts. Biochem J 1989; 259 (02) 585-588
    CrossrefPubMedSearch in Google Scholar
  • 36 Hennerbichler A, Moutos FT, Hennerbichler D, Weinberg JB, Guilak F. Interleukin-1 and tumor necrosis factor alpha inhibit repair of the porcine meniscus in vitro. Osteoarthritis Cartilage 2007; 15 (09) 1053-1060
    CrossrefPubMedSearch in Google Scholar
  • 37 Livshits G, Zhai G, Hart DJ. , et al. Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: the Chingford Study. Arthritis Rheum 2009; 60 (07) 2037-2045
    CrossrefPubMedSearch in Google Scholar
  • 38 Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7 (01) 33-42
    CrossrefPubMedSearch in Google Scholar
  • 39 Merz D, Liu R, Johnson K, Terkeltaub R. IL-8/CXCL8 and growth-related oncogene α/CXCL1 induce chondrocyte hypertrophic differentiation. J Immunol 2003; 171 (08) 4406-4415
    CrossrefPubMedSearch in Google Scholar
  • 40 Ishihara G, Kojima T, Saito Y, Ishiguro N. Roles of metalloproteinase-3 and aggrecanase 1 and 2 in aggrecan cleavage during human meniscus degeneration. Orthop Rev (Pavia) 2009; 1 (02) e14
    CrossrefPubMedSearch in Google Scholar
  • 41 Galloway WA, Murphy G, Sandy JD, Gavrilovic J, Cawston TE, Reynolds JJ. Purification and characterization of a rabbit bone metalloproteinase that degrades proteoglycan and other connective-tissue components. Biochem J 1983; 209 (03) 741-752
    CrossrefPubMedSearch in Google Scholar
  • 42 Little CB, Meeker CT, Golub SB. , et al. Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates cartilage erosion and promotes cartilage repair. J Clin Invest 2007; 117 (06) 1627-1636
    CrossrefPubMedSearch in Google Scholar
  • 43 Nagase H, Kashiwagi M. Aggrecanases and cartilage matrix degradation. Arthritis Res Ther 2003; 5 (02) 94-103
    PubMedSearch in Google Scholar
  • 44 Felson DT, Zhang Y. An update on the epidemiology of knee and hip osteoarthritis with a view to prevention. Arthritis Rheum 1998; 41 (08) 1343-1355
    CrossrefPubMedSearch in Google Scholar
  • 45 Roller BL, Monibi FA, Stoker AM, Kuroki K, Bal BS, Cook JL. Characterization of knee meniscal pathology: correlation of gross, histologic, biochemical, molecular, and radiographic measures of disease. J Knee Surg 2015; 28 (02) 175-182
    Thieme ConnectPubMedSearch in Google Scholar
  • 46 Roller BL, Monibi F, Stoker AM, Bal BS, Cook JL. Identification of novel synovial fluid biomarkers associated with meniscal pathology. J Knee Surg 2016; 29 (01) 47-62
    Thieme ConnectPubMedSearch in Google Scholar
  • 47 Monibi F, Roller BL, Stoker A, Garner B, Bal S, Cook JL. Identification of synovial fluid biomarkers for knee osteoarthritis and correlation with radiographic assessment. J Knee Surg 2016; 29 (03) 242-247
    Thieme ConnectPubMedSearch in Google Scholar
  • 48 Catterall JB, Stabler TV, Flannery CR, Kraus VB. Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254). Arthritis Res Ther 2010; 12 (06) R229
    CrossrefPubMedSearch in Google Scholar
  • 49 Tang Z, Yang L, Wang Y. , et al. Contributions of different intraarticular tissues to the acute phase elevation of synovial fluid MMP-2 following rat ACL rupture. J Orthop Res 2009; 27 (02) 243-248
    CrossrefPubMedSearch in Google Scholar
  • 50 Hellio Le Graverand MP, Eggerer J, Sciore P. , et al. Matrix metalloproteinase-13 expression in rabbit knee joint connective tissues: influence of maturation and response to injury. Matrix Biol 2000; 19 (05) 431-441
    CrossrefPubMedSearch in Google Scholar
  • 51 Fuller ES, Smith MM, Little CB, Melrose J. Zonal differences in meniscus matrix turnover and cytokine response. Osteoarthritis Cartilage 2012; 20 (01) 49-59
    CrossrefPubMedSearch in Google Scholar
  • 52 Stone AV, Loeser RF, Vanderman KS, Long DL, Clark SC, Ferguson CM. Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis. Osteoarthritis Cartilage 2014; 22 (02) 264-274
    CrossrefPubMedSearch in Google Scholar
  • 53 Lemke AK, Sandy JD, Voigt H. , et al. Interleukin-1α treatment of meniscal explants stimulates the production and release of aggrecanase-generated, GAG-substituted aggrecan products and also the release of pre-formed, aggrecanase-generated G1 and m-calpain-generated G1-G2. Cell Tissue Res 2010; 340 (01) 179-188
    CrossrefPubMedSearch in Google Scholar
  • 54 López-Franco M, López-Franco O, Murciano-Antón MA. , et al. Meniscal degeneration in human knee osteoarthritis: in situ hybridization and immunohistochemistry study. Arch Orthop Trauma Surg 2016; 136 (02) 175-183
    CrossrefPubMedSearch in Google Scholar
  • 55 Wang L, Chang G, Bencardino J. , et al. T1rho MRI of menisci in patients with osteoarthritis at 3 Tesla: a preliminary study. J Magn Reson Imaging 2014; 40 (03) 588-595
    CrossrefPubMedSearch in Google Scholar
  • 56 Lohmander LS. Articular cartilage and osteoarthrosis. The role of molecular markers to monitor breakdown, repair and disease. J Anat 1994; 184 (Pt 3): 477-492
    PubMedSearch in Google Scholar
  • 57 Grushko G, Schneiderman R, Maroudas A. Some biochemical and biophysical parameters for the study of the pathogenesis of osteoarthritis: a comparison between the processes of ageing and degeneration in human hip cartilage. Connect Tissue Res 1989; 19 (2-4): 149-176
    CrossrefPubMedSearch in Google Scholar
  • 58 Wheaton AJ, Borthakur A, Shapiro EM. , et al. Proteoglycan loss in human knee cartilage: quantitation with sodium MR imaging--feasibility study. Radiology 2004; 231 (03) 900-905
    CrossrefPubMedSearch in Google Scholar
  • 59 Greenberg DD, Stoker A, Kane S, Cockrell M, Cook JL. Biochemical effects of two different hyaluronic acid products in a co-culture model of osteoarthritis. Osteoarthritis Cartilage 2006; 14 (08) 814-822
    CrossrefPubMedSearch in Google Scholar
  • 60 Cook JL, Kuroki K, Stoker A, Streppa H, Fox DB. Review of in vitro models and development and initial validation of a novel co-culture model for the study of osteoarthritis. Curr Rheumatol Rev 2007; 3 (03) 172-182
    CrossrefPubMedSearch in Google Scholar
  • 61 Hanks BC, Kuroki K, Stoker AM, Cook JL. Evaluation of anti-inflammatory and chondroprotective effects of peroxisome proliferator-activated receptor gamma agonists in cartilage and synovial explants from dogs. Am J Vet Res 2010; 71 (10) 1142-1147
    CrossrefPubMedSearch in Google Scholar
  • 62 Cook JL, Tomlinson JL, Kreeger JM, Cook CR. Induction of meniscal regeneration in dogs using a novel biomaterial. Am J Sports Med 1999; 27 (05) 658-665
    CrossrefPubMedSearch in Google Scholar
  • 63 Franklin SP, Cook JL, Cook CR, Shaikh LS, Clarke KM, Holmes SP. Comparison of ultrasonography and magnetic resonance imaging to arthroscopy for diagnosing medial meniscal lesions in dogs with cranial cruciate ligament deficiency. J Am Vet Med Assoc 2017; 251 (01) 71-79
    CrossrefPubMedSearch in Google Scholar
  • 64 Ritzo ME, Ritzo BA, Siddens AD, Summerlott S, Cook JL. Incidence and type of meniscal injury and associated long-term clinical outcomes in dogs treated surgically for cranial cruciate ligament disease. Vet Surg 2014; 43 (08) 952-958
    CrossrefPubMedSearch in Google Scholar
  • 65 McCready DJ, Ness MG. Systematic review of the prevalence, risk factors, diagnosis and management of meniscal injury in dogs: part 2. J Small Anim Pract 2016; 57 (04) 194-204
    CrossrefPubMedSearch in Google Scholar