• 1.

    Abbas AK. Diseases of immunity. In: Kumar V, Abbas AK, Fausto N, eds. Robbins and Cotran pathologic basis of disease. 7th ed. Philadelphia: Elsevier Saunders, 2004;193267.

    • Search Google Scholar
    • Export Citation
  • 2.

    Papadimitraki ED, Bertsias GK, Boumpas DT. Toll like receptors and autoimmunity: a critical appraisal. J Autoimmun 2007;29:310318.

  • 3.

    Foell D, Wittkowski H, Roth J. Mechanisms of disease: a ‘DAMP’ view of inflammatory arthritis. Nat Clin Pract Rheumatol 2007;3:382390.

    • Search Google Scholar
    • Export Citation
  • 4.

    Marshak-Rothstein A. Toll-like receptors in systemic autoimmune disease. Nat Rev Immunol 2006;6:823835.

  • 5.

    Scanzello CR, Plaas A, Crow MK. Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound? Curr Opin Rheumatol 2008;20:565572.

    • Search Google Scholar
    • Export Citation
  • 6.

    Radstake TR, Roelofs MF, Jenniskens YM, et alExpression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma. Arthritis Rheum 2004;50:38563865.

    • Search Google Scholar
    • Export Citation
  • 7.

    Kim HA, Cho ML, Choi HY, et alThe catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes. Arthritis Rheum 2006;54:21522163.

    • Search Google Scholar
    • Export Citation
  • 8.

    Pond MJ, Nuki G. Experimentally-induced osteoarthritis in the dog. Ann Rheum Dis 1973;32:387388.

  • 9.

    Marijnissen AC, van Roermund PM, TeKoppele JM, et alThe canine ‘groove’ model, compared with the ACLT model of osteoarthritis. Osteoarthritis Cartilage 2002;10:145155.

    • Search Google Scholar
    • Export Citation
  • 10.

    Luther JK, Cook CR, Cook JL. Meniscal release in cruciate ligament intact stifles causes lameness and medial compartment cartilage pathology in dogs 12 weeks postoperatively. Vet Surg 2009;38:520529.

    • Search Google Scholar
    • Export Citation
  • 11.

    Reno C, Marchuk L, Sciore P, et alRapid isolation of total RNA from small samples of hypocellular, dense connective tissues. Biotechniques 1997;22:10821086.

    • Search Google Scholar
    • Export Citation
  • 12.

    Muir P, Schaefer SL, Manley PA, et alExpression of immune response genes in the stifle joint of dogs with oligoarthritis and degenerative cranial cruciate ligament rupture. Vet Immunol Immunopathol 2007;119:214221.

    • Search Google Scholar
    • Export Citation
  • 13.

    Asahina Y, Yoshioka N, Kano R, et alFull-length cDNA cloning of Toll-like receptor 4 in dogs and cats. Vet Immunol Immunopathol 2003;96:159167.

    • Search Google Scholar
    • Export Citation
  • 14.

    Bazzocchi C, Mortarino M, Comazzi S, et alExpression and function of Toll-like receptor 2 in canine blood phagocytes. Vet Immunol Immunopathol 2005;104:1519.

    • Search Google Scholar
    • Export Citation
  • 15.

    Wassef A, Janardhan K, Pearce JW, et alToll-like receptor 4 in normal and inflamed lungs and other organs of pig, dog and cattle. Histol Histopathol 2004;19:12011208.

    • Search Google Scholar
    • Export Citation
  • 16.

    Venable RO, Stoker AM, Cook CR, et alExamination of synovial fluid hyaluronan quantity and quality in stifle joints of dogs with osteoarthritis. Am J Vet Res 2008;69:15691573.

    • Search Google Scholar
    • Export Citation
  • 17.

    Noble PW, Jiang D. Matrix regulation of lung injury, inflammation, and repair: the role of innate immunity. Proc Am Thorac Soc 2006;3:401404.

    • Search Google Scholar
    • Export Citation
  • 18.

    Fieber C, Baumann P, Vallon R, et alHyaluronan-oligosaccharide-induced transcription of metalloproteases. J Cell Sci 2004;117:359367.

  • 19.

    Gariboldi S, Palazzo M, Zanobbio L, et alLow molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of B-defensin 2 via TLR2 and TLR4. J Immunol 2008;181:21032110.

    • Search Google Scholar
    • Export Citation
  • 20.

    Taylor KR, Trowbridge JM, Rudisill JA, et alHyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem 2004;279:1707917084.

    • Search Google Scholar
    • Export Citation
  • 21.

    Voelcker V, Gebhardt C, Averbeck M, et alHyaluronan fragments induce cytokine and metalloprotease upregulation in human melanoma cells in part by signaling via TLR4. Exp Dermatol 2008;17:100107.

    • Search Google Scholar
    • Export Citation
  • 22.

    Bobacz K, Sunk IG, Hofstaetter JG, et alToll-like receptors and chondrocytes: the lipopolysaccharide-induced decrease in cartilage matrix synthesis is dependent on the presence of toll-like receptor 4 and antagonized by bone morphogenetic protein 7. Arthritis Rheum 2007;56:18801893.

    • Search Google Scholar
    • Export Citation
  • 23.

    Glasson SS, Blanchet TJ, Morris EA. The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse. Osteoarthritis Cartilage 2007;15:10611069.

    • Search Google Scholar
    • Export Citation
  • 24.

    Frost-Christensen LN, Mastbergen SC, Vianen ME, et alDegeneration, inflammation, regeneration, and pain/disability in dogs following destabilization or articular cartilage grooving of the stifle joint. Osteoarthritis Cartilage 2008;16:13271335.

    • Search Google Scholar
    • Export Citation
  • 25.

    Vergunst CE, van de Sande MG, Lebre MC, et alThe role of chemokines in rheumatoid arthritis and osteoarthritis. Scand J Rheumatol 2005;34:415425.

    • Search Google Scholar
    • Export Citation
  • 26.

    Borzi RM, Mazzetti I, Macor S, et alFlow cytometric analysis of intracellular chemokines in chondrocytes in vivo: constitutive expression and enhancement in osteoarthritis and rheumatoid arthritis. FEBS Lett 1999;455:238242.

    • Search Google Scholar
    • Export Citation
  • 27.

    Saito I, Koshino T, Nakashima K, et alIncreased cellular infiltrate in inflammatory synovia of osteoarthritic knees. Osteoarthritis Cartilage 2002;10:156162.

    • Search Google Scholar
    • Export Citation
  • 28.

    Revell PA, Mayston V, Lalor P, et alThe synovial membrane in osteoarthritis: a histological study including the characterization of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal antibodies. Ann Rheum Dis 1988;47:300307.

    • Search Google Scholar
    • Export Citation

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Expression of Toll-like receptors 2 and 4 in stifle joint synovial tissues of dogs with or without osteoarthritis

Keiichi Kuroki DVM, PhD1, Aaron M. Stoker PhD2, Hannah J. Sims BS3, and James L. Cook DVM, PhD4
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  • 1 Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO 65211.
  • | 2 Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO 65211.
  • | 3 Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO 65211.
  • | 4 Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO 65211.

Abstract

Objective—To investigate the presence or absence of Toll-like receptor (TLR)-2 and TLR-4 in synovial tissues collected from stifle joints (SJs) of dogs with or without osteoarthritis.

Animals—21 purpose-bred research dogs, 3 client-owned dogs with SJ osteoarthritis, and 3 dogs without SJ osteoarthritis.

Procedures—Research dogs underwent arthroscopic surgery in 1 SJ to induce osteoarthritis via cranial cruciate ligament transection (CrCLt; n = 5), femoral condylar articular cartilage groove creation (6), or release of the caudal horn of the medial meniscus (5); 5 dogs underwent sham surgery. Synovial tissue specimens were obtained from both stifle joints of each dog 12 weeks after surgery, and TLR-2 and TLR-4 gene expression were determined via real-time reverse transcription PCR assays. Expression of TLR-4 protein was determined via an immunofluorescence technique in additional specimens obtained from osteoarthritic SJs of dogs with cranial cruciate ligament insufficiency and from dogs with nonosteoarthritic SJs.

Results—Synovial tissues from CrCLt-treated joints had significantly higher TLR-4 gene expression, compared with the contralateral control SJs or any other joint group. TLR-2 gene expression did not differ significantly among groups. Toll-like receptor-4 protein was detected in synovial tissues of osteoarthritic SJs but was rarely evident in nonosteoarthritic SJs.

Conclusions and Clinical Relevance—Increased TLR-4 gene expression in the synovial tissue of SJs with osteoarthritis secondary to CrCLt suggests that activation of innate immunity may play a role in the pathophysiology of SJ osteoarthritis in at least a subset of dogs.

Contributor Notes

This study was performed in conjunction with research funded by Pfizer Animal Health.

Address correspondence to Dr. Kuroki (kurokik@missouri.edu).