Editorial Type:
Bone, Joint, and Cartilage

High-mobility group box chromosomal protein 1 as a potential inflammatory biomarker of joint injury in Thoroughbreds

Murray P. Brown Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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 DVM, MSc
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Troy N. Trumble Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108.

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 DVM, PhD
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Kelly A. Merritt Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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DOI:
https://doi.org/10.2460/ajvr.70.10.1230
Volume/Issue:
Volume 70: Issue 10
Online Publication Date:
01 Oct 2009
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Abstract

Objective—To investigate effects of osteochondral injury on high-mobility group box chromosomal protein 1 (HMGB-1) concentrations in synovial fluid (SF) from Thoroughbreds and to compare these results with radiographic and arthroscopic scores of severity of joint injury.

Animals—40 clinically normal rested Thoroughbreds (group 1) and 45 Thoroughbreds with osteochondral injury as a result of racing.

Procedures—SF was obtained from the metacarpophalangeal (MCP) joints, metatarsophalangeal (MTP) joints, middle carpal joints, and radiocarpal joints. For group 2, radiographic and arthroscopic scores were determined. Concentrations of SF HMGB-1 were determined by use of an ELISA.

Results—SF HMGB-1 concentrations in osteochondral-injured MCP-MTP joints were significantly higher than in normal MCP-MTP joints. Similarly, SF HMGB-1 concentrations in osteochondral-injured carpal joints were significantly higher than in normal carpal joints. Radiographic and arthroscopic scores were not correlated with SF HMGB-1 concentrations. Synovial fluid HMGB-1 concentrations ≥ 11 ng/mL for MCP-MTP joints and ≥ 9 ng/mL for carpal joints discriminated osteochondral-injured joints from normal joints. Horses with HMGB-1 concentrations ≥ 11 ng/mL for MCP-MTP joints were twice as likely to have an osteochondral injury, and horses with HMGB-1 concentrations ≥ 9 ng/mL for carpal joints were 4 times as likely to have an osteochondral injury.

Conclusions and Clinical Relevance—Osteochondral injury was associated with a significant increase in SF HMGB-1 concentrations in MCP-MTP and carpal joints, compared with results for clinically normal Thoroughbreds. Analysis of SF HMGB-1 concentrations may be useful for evaluation of joint injury in horses.

Abstract

Objective—To investigate effects of osteochondral injury on high-mobility group box chromosomal protein 1 (HMGB-1) concentrations in synovial fluid (SF) from Thoroughbreds and to compare these results with radiographic and arthroscopic scores of severity of joint injury.

Animals—40 clinically normal rested Thoroughbreds (group 1) and 45 Thoroughbreds with osteochondral injury as a result of racing.

Procedures—SF was obtained from the metacarpophalangeal (MCP) joints, metatarsophalangeal (MTP) joints, middle carpal joints, and radiocarpal joints. For group 2, radiographic and arthroscopic scores were determined. Concentrations of SF HMGB-1 were determined by use of an ELISA.

Results—SF HMGB-1 concentrations in osteochondral-injured MCP-MTP joints were significantly higher than in normal MCP-MTP joints. Similarly, SF HMGB-1 concentrations in osteochondral-injured carpal joints were significantly higher than in normal carpal joints. Radiographic and arthroscopic scores were not correlated with SF HMGB-1 concentrations. Synovial fluid HMGB-1 concentrations ≥ 11 ng/mL for MCP-MTP joints and ≥ 9 ng/mL for carpal joints discriminated osteochondral-injured joints from normal joints. Horses with HMGB-1 concentrations ≥ 11 ng/mL for MCP-MTP joints were twice as likely to have an osteochondral injury, and horses with HMGB-1 concentrations ≥ 9 ng/mL for carpal joints were 4 times as likely to have an osteochondral injury.

Conclusions and Clinical Relevance—Osteochondral injury was associated with a significant increase in SF HMGB-1 concentrations in MCP-MTP and carpal joints, compared with results for clinically normal Thoroughbreds. Analysis of SF HMGB-1 concentrations may be useful for evaluation of joint injury in horses.

Contributor Notes

Supported in part by the College of Veterinary Medicine of the University of Florida and the Office of the Dean of the Graduate School of the University of Minnesota.

Published as journal series No. 656 of the University of Florida, College of Veterinary Medicine.

Address correspondence to Dr. Brown (brownmu@vetmed.ufl.edu).
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Oct 2009
  • 1.

    Goodwin GH, Sanders C, Johns EW. A new group of chromatin-associated proteins with a high content of acidic and basic amino acids. Eur J Biochem 1973;38:14–19.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999;285:248–251.

  • 3.

    Yang H, Wang H, Czura CJ, et al. The cytokine activity of HMGB1. J Leukoc Biol 2005;78:1–8.

  • 4.

    Kokkola R, Sundberg E, Ulfgren AK, et al. High mobility group box chromosomal protein 1: a novel proinflammatory mediator in synovitis. Arthritis Rheum 2002;46:2598–2603.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Wittemann B, Neuer G, Michels H, et al. Autoantibodies to nonhistone chromosomal proteins HMG-1 and HMG-2 in sera of patients with juvenile rheumatoid arthritis. Arthritis Rheum 1990;33:1378–1383.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Palmblad K, Sundberg E, Diez M, et al. Morphological characterization of intra-articular HMGB1 expression during the course of collagen-induced arthritis. Arthritis Res Ther 2007;9:R35–R45.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Kokkola R, Andersson A, Mullins G, et al. RAGE is the major receptor for the proinflammatory activity of HMGB1 in rodent macrophages. Scand J Immunol 2005;61:1–9.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Pullerits R, Jonsson IM, Verdrengh M, et al. High mobility group box chromosomal protein 1, a DNA binding cytokine, induces arthritis. Arthritis Rheum 2003;48:1693–1700.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Taniguchi N, Kawahara K, Yone K, et al. High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum 2003;48:971–981.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Hamada T, Torikai M, Kuwazuru A, et al. Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis. Arthritis Rheum 2008;58:2675–2685.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Elders MJ. The increasing impact of arthritis on public health. J Rheumatol Suppl 2000;60:6–8.

  • 12.

    Garnero P, Delmas PD. Biomarkers in osteoarthritis. Curr Opin Rheumatol 2003;15:641–646.

  • 13.

    Brown MP, Trumble TN, Plaas AH, et al. Exercise and injury increase chondroitin sulfate chain length and decrease hyaluronan chain length in synovial fluid. Osteoarthritis Cartilage 2007;15:1318–1325.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Frisbie DD, Ray CS, Ionescu M, et al. Measurement of synovial fluid and serum concentrations of the 846 epitope of chondroitin sulfate and of carboxy propeptides of type II procollagen for diagnosis of osteochondral fragmentation in horses. Am J Vet Res 1999;60:306–309.

    • Search Google Scholar
    • Export Citation
  • 15.

    Fuller CJ, Barr AR, Sharif M, et al. Cross-sectional comparison of synovial fluid biochemical markers in equine osteoarthritis and the correlation of these markers with articular cartilage damage. Osteoarthritis Cartilage 2001;9:49–55.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Trumble TN, Brown MP, Merritt KA, et al. Joint dependent concentrations of bone alkaline phosphatase in serum and synovial fluids of horses with osteochondral injury: an analytical and clinical validation. Osteoarthritis Cartilage 2008;16:779–786.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    van den Boom R, van de Lest CH, Bull S, et al. Influence of repeated arthrocentesis and exercise on synovial fluid concentrations of nitric oxide, prostaglandin E2 and glycosaminoglycans in healthy equine joints. Equine Vet J 2005;37:250–256.

    • Search Google Scholar
    • Export Citation
  • 18.

    McIlwraith CW, Yovich JV, Martin GS. Arthroscopic surgery for the treatment of osteochondral chip fractures in the equine carpus. J Am Vet Med Assoc 1987;191:531–540.

    • Search Google Scholar
    • Export Citation
  • 19.

    Yovich JV, McIlwraith CW. Arthroscopic surgery for osteochondral fractures of the proximal phalanx of the metacarpophalangeal and metatarsophalangeal (fetlock) joints in horses. J Am Vet Med Assoc 1986;188:273–279.

    • Search Google Scholar
    • Export Citation
  • 20.

    Chen G, Ward MF, Sama AE, et al. Extracellular HMGB1 as a proinflammatory cytokine. J Interferon Cytokine Res 2004;24:329–333.

  • 21.

    Andersson U, Wang H, Palmblad K, et al. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med 2000;192:565–570.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Rendon-Mitchell B, Ochani M, Li J, et al. IFN-gamma induces high mobility group box 1 protein release partly through a TNFdependent mechanism. J Immunol 2003;170:3890–3897.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Bondeson J, Wainwright SD, Lauder S, et al. 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–R199.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Trumble TN, Scarbrough AB, Brown MP. Osteochondral injury increases type II collagen degradation products (C2C) in synovial fluid of Thoroughbred racehorses. Osteoarthritis Cartilage 2009;17:371–374.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Beertsen W, van den Bos T. Alkaline phosphatase induces the mineralization of sheets of collagen implanted subcutaneously in the rat. J Clin Invest 1992;89:1974–1980.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Li W, Li J, Ashok M, et al. A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinflammatory mediator, high mobility group box 1. J Immunol 2007;178:3856–3864.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    af Klint E, Grundtman C, Engstrom M, et al. Intraarticular glucocorticoid treatment reduces inflammation in synovial cell infiltrations more efficiently than in synovial blood vessels. Arthritis Rheum 2005;52:3880–3889.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Thakur MK, Prasad S. Analysis of age-associated alteration in the synthesis of HMG nonhistone proteins of the rat liver. Mol Biol Rep 1991;15:19–24.

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