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Research in veterinary science2008; 86(3); 490-497; doi: 10.1016/j.rvsc.2008.10.008

Interleukin-6 and high mobility group box protein-1 in synovial membranes and osteochondral fragments in equine osteoarthritis.

Abstract: Cytokine production in synovial membranes (SM) and osteochondral fragments (OCF) may influence the development of equine osteoarthritis (OA). In this study, the presence of interleukin (IL)-6 and cytoplasmic and extracellular high mobility group box protein (HMGB)-1 in SM and osteochondral tissue from healthy and diseased equine joints was investigated by immunohistochemistry. Additionally, microscopic synovitis was graded. IL-6 was commonly found in SM cells and in chondrocytes in uncalcified cartilage of OCF, whereas little staining was detected in healthy cartilage. Cytoplasmic and/or extracellular HMGB-1 was widespread only in SM from diseased joints, and also detected in OCF in areas of cartilage damage, fibrous repair tissue, and tidemark reduplication. Joints with OCF and cartilage lesions (without OCF) showed significantly higher median synovitis scores than healthy joints (p=0.013 and p=0.042, respectively). The study identifies OCF as a source of inflammatory mediators in equine OA, as shown by the presence of IL-6 and extracellular HMGB-1 in the fragment. Based upon HMGB-1 release in SM and OCF, further studies to investigate possible involvement of HMGB-1 in the pathogenesis of OA are warranted.
Publication Date: 2008-11-29 PubMed ID: 19041991DOI: 10.1016/j.rvsc.2008.10.008Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research involves exploring the presence and impact of specific cytokines, namely interleukin-6 (IL-6) and high mobility group box protein-1 (HMGB-1), in the development of equine osteoarthritis (OA). The study revealed that these cytokines were often found in unhealthy tissue, highlighting the possibility that they could play a critical role in the onset and progression of OA in horses.

Objective of the Study

  • This study aimed to examine the presence of interleukin (IL)-6 and high mobility group box protein (HMGB-1) in the synovial membranes (SM) and osteochondral fragments (OCF) from healthy and diseased equine joints.

Methodology and Findings

  • The researchers used immunohistochemistry, a technique that uses antibodies to detect specific proteins in cells of a tissue section, to locate the presence of IL-6 and HMGB-1 in the samples.
  • They observed that IL-6 was commonly found in cells within the synovial membranes and in chondrocytes – specialized cells that generate and maintain the cartilage matrix – of uncalcified cartilage within the osteochondral fragments. Less of the cytokine was detected in healthy cartilage.
  • Additionally, they located HMGB-1, either within the cell (cytoplasmic) or outside of the cell (extracellular), mainly in the synovial membranes of diseased joints and in areas of cartilage damage, repair tissue, and tidemark duplication within the osteochondral fragments.

Results and Implications

  • The research documented that joints with osteochondral fragments – and those with cartilage lesions but no fragments – displayed higher synovitis scores than healthy joints. Synovitis is the inflammation of the synovial membrane, a layer of connective tissue that lines the joints. This finding signifies greater inflammation and disease activity within these joints.
  • The study underscored the role of osteochondral fragments as a source of inflammatory mediators in equine osteoarthritis, evident by the presence of IL-6 and extracellular HMGB-1 in these fragments.
  • The report suggested the necessity for further investigations into the potential involvement of HMGB-1 in the progression of OA due to its notable release in both the synovial membrane and the osteochondral fragments.

Cite This Article

APA
Ley C, Ekman S, Ronéus B, Eloranta ML. (2008). Interleukin-6 and high mobility group box protein-1 in synovial membranes and osteochondral fragments in equine osteoarthritis. Res Vet Sci, 86(3), 490-497. https://doi.org/10.1016/j.rvsc.2008.10.008

Publication

ISSN: 0034-5288
NlmUniqueID: 0401300
Country: England
Language: English
Volume: 86
Issue: 3
Pages: 490-497

Researcher Affiliations

Ley, C
  • Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden. cecilia.ley@bvf.slu.se
Ekman, S
    Ronéus, B
      Eloranta, M-L

        MeSH Terms

        • Aging / physiology
        • Animals
        • Arthroscopy / methods
        • Arthroscopy / veterinary
        • HMGB1 Protein / metabolism
        • Horse Diseases / metabolism
        • Horse Diseases / pathology
        • Horse Diseases / surgery
        • Horses
        • Interleukin-6 / metabolism
        • Joints / metabolism
        • Joints / pathology
        • Osteoarthritis / metabolism
        • Osteoarthritis / pathology
        • Osteoarthritis / surgery
        • Osteoarthritis / veterinary
        • Osteochondritis / metabolism
        • Osteochondritis / pathology
        • Osteochondritis / veterinary
        • Reference Values

        Citations

        This article has been cited 8 times.
        1. Li W, Tao C, Mao M, Zhu K. The Nrf2/HMGB1/NF-κB axis modulates chondrocyte apoptosis and extracellular matrix degradation in osteoarthritis. Acta Biochim Biophys Sin (Shanghai) 2023 May 26;55(5):818-830.
          doi: 10.3724/abbs.2023078pubmed: 37232576google scholar: lookup
        2. Chattopadhyay H, Auddy B, Sur T, Gupta M, Datta S. Transdermal co-delivery of glucosamine sulfate and diacerein for the induction of chondroprotection in experimental osteoarthritis. Drug Deliv Transl Res 2020 Oct;10(5):1327-1340.
          doi: 10.1007/s13346-019-00701-7pubmed: 31907788google scholar: lookup
        3. Wang Y, Shen S, Li Z, Li W, Weng X. MIR-140-5p affects chondrocyte proliferation, apoptosis, and inflammation by targeting HMGB1 in osteoarthritis. Inflamm Res 2020 Jan;69(1):63-73.
          doi: 10.1007/s00011-019-01294-0pubmed: 31712854google scholar: lookup
        4. Wenzhao L, Jiangdong N, Deye S, Muliang D, Junjie W, Xianzhe H, Mingming Y, Jun H. Dual regulatory roles of HMGB1 in inflammatory reaction of chondrocyte cells and mice. Cell Cycle 2019 Sep;18(18):2268-2280.
          doi: 10.1080/15384101.2019.1642680pubmed: 31313630google scholar: lookup
        5. Malemud CJ. Recent advances in neutralizing the IL-6 pathway in arthritis. Open Access Rheumatol 2009;1:133-150.
          doi: 10.2147/oarrr.s6266pubmed: 27789987google scholar: lookup
        6. Wang X, Guo Y, Wang C, Yu H, Yu X, Yu H. MicroRNA-142-3p Inhibits Chondrocyte Apoptosis and Inflammation in Osteoarthritis by Targeting HMGB1. Inflammation 2016 Oct;39(5):1718-28.
          doi: 10.1007/s10753-016-0406-3pubmed: 27447821google scholar: lookup
        7. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol 2010 Nov;6(11):625-35.
          doi: 10.1038/nrrheum.2010.159pubmed: 20924410google scholar: lookup
        8. El-Deeb WM, El-Bahr SM. Investigation of selected biochemical indicators of Equine Rhabdomyolysis in Arabian horses: pro-inflammatory cytokines and oxidative stress markers. Vet Res Commun 2010 Dec;34(8):677-89.
          doi: 10.1007/s11259-010-9439-5pubmed: 20830520google scholar: lookup