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Journal of proteomics2019; 202; 103370; doi: 10.1016/j.jprot.2019.04.020

The synovial fluid proteome differentiates between septic and nonseptic articular pathologies.

Abstract: Articular conditions are common in horses and can result in loss of function, chronic pain and/or inability to work. Common conditions include osteoarthritis, osteochondrosis and synovial sepsis, which can be life-threatening, but despite the high clinical prevalence of these conditions, rapid and specific diagnosis, monitoring and prognostication remains a challenge for practicing veterinarians. Synovial fluid from a range of arthropathies was enriched for low abundance proteins using combinatorial peptide ligand ProteoMiner™ beads and analysed via liquid chromatography-tandem mass spectrometry. Changes in protein abundances were analysed using label-free quantification. Principle component analysis of differentially expressed proteins identified groupings associated with joint pathology. Findings were validated using ELISA. Lactotransferrin (LTF) abundance was increased in sepsis compared to all other groups and insulin-like growth factor-binding protein 6 (IGFBP6) abundance decreased in sepsis compared to other disease groups. Pathway analysis identified upregulation of the complement system in synovial joint sepsis and the downregulation of eukaryotic translation initiation factors and mTOR signalling pathways in both OA and OC compared to the healthy group. Overall, we have identified a catalogue of proteins which we propose to be involved in osteoarthritis, osteochondrosis and synovial sepsis pathogenesis. SIGNIFICANCE: Osteoarthritis, osteochondrosis and synovial sepsis, which can be life-threatening, are common articular conditions in which rapid and specific diagnosis, monitoring and prognostication remains a challenge for practicing veterinarians. This study has identified that the equine synovial fluid proteome exhibits distinctive profile changes between osteoarthritis, osteochondrosis, synovial sepsis and healthy joints. Elevated synovial abundance of lactotransferrin and decreased insulin-like growth factor-binding protein 6 were both found to distinguish synovial sepsis from all other study groups. Thus, these protein markers may have a future role in clinical practice to enable an earlier and reliable diagnosis of synovial sepsis.
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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Publication Date: 2019-04-25 PubMed ID: 31028944PubMed Central: PMC6549134DOI: 10.1016/j.jprot.2019.04.020Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research focused on identifying clear distinction between septic and nonseptic joint conditions in horses by studying the synovial fluid proteome. The team found unique protein markers that could aid in the earlier and more reliable diagnosis of synovial sepsis.

Objective and Methodology of the Study

  • The study was aimed at discerning between septic and nonseptic joint conditions in horses, such as osteoarthritis, osteochondrosis and synovial sepsis. The current challenge for veterinarians is an efficient and exact diagnosis, monitoring, and prognosis of these conditions.
  • Synovial fluid from different arthropathies was enriched using ProteoMiner™ beads (designed for low abundance proteins) and was analyzed via liquid chromatography-tandem mass spectrometry.
  • The researchers analyzed the change in protein abundances using label-free quantification. By performing a principle component analysis of the differentially expressed proteins, the researchers were able to associate specific groupings with joint pathologies.

Findings of the Study

  • The study observed that Lactotransferrin (LTF) abundance was notably increased in sepsis as compared to all other groups whereas the abundance of insulin-like growth factor-binding protein 6 (IGFBP6) was decreased in sepsis compared to other disease groups.
  • In addition to this, an upregulation of the complement system in synovial joint sepsis was observed.
  • Downregulation of eukaryotic translation initiation factors and mTOR signalling pathways was observed in both osteoarthritis (OA) and osteochondrosis (OC) when compared to the healthy group. This indicates a possible involvement of these pathways in the pathogenesis of these conditions.
  • Overall, the study identified a catalogue of proteins hypothesized to be involved in the pathogenesis of osteoarthritis, osteochondrosis and synovial sepsis.

Significance of the Research

  • This research could be groundbreaking for veterinary medicine in terms of diagnosing equine joint conditions like osteoarthritis, osteochondrosis and synovial sepsis.
  • The findings suggest distinct changes in the synovial fluid protein composition between healthy joints and those afflicted with the aforementioned diseases. The elevated presence of Lactotransferrin and reduced levels of insulin-like growth factor-binding protein 6 were found to distinguish synovial sepsis from the other conditions.
  • This distinction could provide veterinary professionals with clear, biological markers for the early and reliable diagnosis of synovial sepsis, improving prognosis and treatment outcomes.

Cite This Article

APA
Anderson JR, Smagul A, Simpson D, Clegg PD, Rubio-Martinez LM, Peffers MJ. (2019). The synovial fluid proteome differentiates between septic and nonseptic articular pathologies. J Proteomics, 202, 103370. https://doi.org/10.1016/j.jprot.2019.04.020

Publication

Journal of proteomics
ISSN: 1876-7737
NlmUniqueID: 101475056
Country: Netherlands
Language: English
Volume: 202
Pages: 103370

Researcher Affiliations

Anderson, James R
  • Institute of Ageing and Chronic Disease, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, UK. Electronic address: janders@liverpool.ac.uk.
Smagul, Aibek
  • Institute of Ageing and Chronic Disease, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, UK. Electronic address: aibek@liverpool.ac.uk.
Simpson, Deborah
  • Centre for Proteome Research, Institute of Integrative Biology, Biosciences Building, Crown Street, University of Liverpool, Liverpool L69 7ZB, UK. Electronic address: dsimpson@liverpool.ac.uk.
Clegg, Peter D
  • Institute of Ageing and Chronic Disease, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, UK. Electronic address: pclegg@liverpool.ac.uk.
Rubio-Martinez, Luis M
  • Department of Equine Clinical Studies, Institute of Veterinary Science, Chester High Road, Neston CH64 7TE, UK. Electronic address: lrubio@liverpool.ac.uk.
Peffers, Mandy J
  • Institute of Ageing and Chronic Disease, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, UK. Electronic address: peffs@liv.ac.uk.

MeSH Terms

  • Animals
  • Biomarkers / metabolism
  • Horse Diseases / metabolism
  • Horses / metabolism
  • Osteoarthritis / metabolism
  • Osteoarthritis / veterinary
  • Proteomics
  • Synovial Fluid / metabolism

Grant Funding

  • Wellcome Trust
  • MR/P020941/1 / Medical Research Council

References

This article includes 46 references
  1. Rubio-Martinez L.M., Elmas C.R., Black B., Monteith G.. Clinical use of antimicrobial regional limb perfusion in horses: 174 cases (1999-2009). J. Am. Vet. Med. Assoc. 2012;241:1650–1658.
    pubmed: 23216042
  2. Dicker K.T., Gurski L.A., Pradhan-Bhatt S., Witt R.L., Farach-Carson M.C., Jia X.. Hyaluronan: a simple polysaccharide with diverse biological functions. Acta Biomater. 2014;10:1558–1570.
    pmc: PMC3960342pubmed: 24361428
  3. Ruiz-Romero C., Blanco F.J.. Proteomics role in the search for improved diagnosis, prognosis and treatment of osteoarthritis. Osteoarthr. Cartil. 2010;18:500–509.
    pubmed: 20060947
  4. Mateos J., Lourido L., Fernandez-Puente P., Calamia V., Fernandez-Lopez C., Oreiro N.. Differential protein profiling of synovial fluid from rheumatoid arthritis and osteoarthritis patients using LC-MALDI TOF/TOF. J. Proteome. 2012;75:2869–2878.
    pubmed: 22245418
  5. Frisbie D.D.. Synovial joint biology and pathobiology. In: Stick JAAaJA, editor. Equine Surgery. 3rd ed. Elsevier Inc; St. Louis: 2006. pp. 1036–1055.
  6. Sanchez-Teran A.F., Bracamonte J.L., Hendrick S., Riddell L., Musil K., Hoff B.. Effect of repeated through-and-through joint lavage on serum amyloid a in synovial fluid from healthy horses. Vet. J. 2016;210:30–33.
    pubmed: 26831179
  7. Jacobsen S., Thomsen M.H., Nanni S.. Concentrations of serum amyloid a in serum and synovial fluid from healthy horses and horses with joint disease. Am. J. Vet. Res. 2006;67:1738–1742.
    pubmed: 17014325
  8. Sinovich M., Villarino N.F., Singer E.R., Robinson C.S., Rubio-Martinez L.M.. Investiagtion of blood serum amyloid a concentrations in horses to differentiate synovial sepsis from inflammation and determine prognosis an response to treatment. Vet. Surg. 2018;47:E26.
    pmc: PMC7591800pubmed: 32098906
  9. Peffers M.J., McDermott B., Clegg P.D., Riggs C.M.. Comprehensive protein profiling of synovial fluid in osteoarthritis following protein equalization. Osteoarthr. Cartil. 2015;23:1204–1213.
    pmc: PMC4528073pubmed: 25819577
  10. Jacobsen S., Niewold T.A., Halling-Thomsen M., Nanni S., Olsen E., Lindegaard C.. Serum amyloid a isoforms in serum and synovial fluid in horses with lipopolysaccharide-induced arthritis. Vet. Immunol. Immunopathol. 2006;110:325–330.
    pubmed: 16337010
  11. Robinson C.S., Singer E.R., Piviani M., Rubio-Martinez L.M.. Are serum amyloid A or D-lactate useful to diagnose synovial contamination or sepsis in horses?. Vet. Rec. 2017;181:425.
    pmc: PMC5738594pubmed: 28765498
  12. McIlwraith C.W., Frisbie D.D., Kawcak C.E., Fuller C.J., Hurtig M., Cruz A.. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the horse. Osteoarthr. Cartil. 2010;18(Suppl. 3):S93–105.
    pubmed: 20864027
  13. Vizcaino J.A., Csordas A., del-Toro N., Dianes J.A., Griss J., Lavidas I.. 2016 update of the PRIDE database and its related tools. Nucleic Acids Res. 2016;44:D447–D456.
    pmc: PMC4702828pubmed: 26527722
  14. Albar A.H., Almehdar H.A., Uversky V.N., Redwan E.M.. Structural heterogeneity and multifunctionality of lactoferrin. Curr. Protein Pept. Sci. 2014;15:778–797.
    pubmed: 25245670
  15. Paramasivam M., Saravanan K., Uma K., Sharma S., Singh T.P., Srinivasan A.. Expression, purification, and characterization of equine lactoferrin in Pichia pastoris. Protein Expr. Purif. 2002;26:28–34.
    pubmed: 12356467
  16. Ye Q., Zheng Y., Fan S., Qin Z., Li N., Tang A.. Lactoferrin deficiency promotes colitis-associated colorectal dysplasia in mice. PLoS One 2014;9.
    pmc: PMC4110006pubmed: 25057912
  17. Edde L., Hipolito R.B., Hwang F.F., Headon D.R., Shalwitz R.A., Sherman M.P.. Lactoferrin protects neonatal rats from gut-related systemic infection. Am. J. Physiol. Gastrointest. Liver Physiol. 2001;281:G1140–G1150.
    pubmed: 11668022
  18. Nibbering P.H., Ravensbergen E., Welling M.M., van Berkel L.A., van Berkel P.H., Pauwels E.K.. Human lactoferrin and peptides derived from its N terminus are highly effective against infections with antibiotic-resistant bacteria. Infect. Immun. 2001;69:1469–1476.
    pmc: PMC98043pubmed: 11179314
  19. Pammi M., Abrams S.A.. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst. Rev. 2015;(2):1–51. (CD007137).
    pubmed: 25699678
  20. Valenti P., Antonini G.. Lactoferrin: an important host defence against microbial and viral attack. Cell. Mol. Life Sci. 2005;62:2576–2587.
    pmc: PMC11139069pubmed: 16261253
  21. Afeltra A., Caccavo D., Ferri G.M., Addessi M.A., De Rosa F.G., Amoroso A.. Expression of lactoferrin on human granulocytes: analysis with polyclonal and monoclonal antibodies. Clin. Exp. Immunol. 1997;109:279–285.
    pmc: PMC1904733pubmed: 9276523
  22. Bennett R.M., Skosey J.L.. Lactoferrin and lysozyme levels in synovial fluid: differential indices of articular inflammation and degradation. Arthritis Rheum. 1977;20:84–90.
    pubmed: 836340
  23. Abbink J.J., Kamp A.M., Nieuwenhuys E.J., Nuijens J.H., Swaak A.J., Hack C.E.. Predominant role of neutrophils in the inactivation of alpha 2-macroglobulin in arthritic joints. Arthritis Rheum. 1991;34:1139–1150.
    pubmed: 1718287
  24. Caccavo D., Garzia P., Sebastiani G.D., Ferri G.M., Galluzzo S., Vadacca M.. Expression of lactoferrin on neutrophil granulocytes from synovial fluid and peripheral blood of patients with rheumatoid arthritis. J. Rheumatol. 2003;30:220–224.
    pubmed: 12563671
  25. Decoteau E, Yurchak AM, Partridge RE, Tomasi TB, Jr.. Lactoferrin in synovial fluid of patients with inflammatory arthritis. Arthritis Rheum. 1972;15:324–5.
    pubmed: 4555646
  26. Zhang C., Li Y., Tang W., Kamiya N., Kim H.. Lactoferrin activates BMP7 gene expression through the mitogen-activated protein kinase ERK pathway in articular cartilage. Biochem. Biophys. Res. Commun. 2013;431:31–35.
    pubmed: 23296204
  27. Shirtliff M.E., Mader J.T.. Acute septic arthritis. Clin. Microbiol. Rev. 2002;15:527–544.
    pmc: PMC126863pubmed: 12364368
  28. Baveye S., Elass E., Mazurier J., Spik G., Legrand D.. Lactoferrin: a multifunctional glycoprotein involved in the modulation of the inflammatory process. Clin. Chem. Lab. Med. 1999;37:281–286.
    pubmed: 10353473
  29. Baynes R.D., Bezwoda W.R.. Lactoferrin and the inflammatory response. Adv. Exp. Med. Biol. 1994;357:133–141.
    pubmed: 7762425
  30. Kruzel M.L., Harari Y., Mailman D., Actor J.K., Zimecki M.. Differential effects of prophylactic, concurrent and therapeutic lactoferrin treatment on LPS-induced inflammatory responses in mice. Clin. Exp. Immunol. 2002;130:25–31.
    pmc: PMC1906493pubmed: 12296849
  31. Alunno A., Bistoni O., Manetti M., Cafaro G., Valentini V., Bartoloni E.. Insulin-like growth factor binding protein 6 in rheumatoid arthritis: a possible novel chemotactic factor?. Front. Immunol. 2017;8:554.
    pmc: PMC5435743pubmed: 28572803
  32. Aboalola D., Han V.K.M.. Different effects of insulin-like growth Factor-1 and insulin-like growth Factor-2 on myogenic differentiation of human mesenchymal stem cells. Stem Cells Int. 2017;2017:8286248.
    pmc: PMC5745708pubmed: 29387091
  33. Nedic O., Robajac D., Sunderic M., Miljus G., Dukanovic B., Malenkovic V.. Detection and identification of oxidized insulin-like growth factor-binding proteins and receptors in patients with colorectal carcinoma. Free Radic. Biol. Med. 2013;65:1195–1200.
    pubmed: 24051179
  34. Lu S., Purohit S., Sharma A., Zhi W., He M., Wang Y.. Serum insulin-like growth factor binding protein 6 (IGFBP6) is increased in patients with type 1 diabetes and its complications. Int. J. Clin. Exp. Med. 2012;5:229–237.
    pmc: PMC3403553pubmed: 22837797
  35. Anderson J.R., Phelan M.M., Clegg P.D., Peffers M.J., Rubio-Martinez L.M.. Synovial fluid metabolites differentiate between septic and nonseptic joint pathologies. J. Proteome Res. 2018;17:2735–2743.
    pmc: PMC6092013pubmed: 29969035
  36. Levi M., Keller T.T., van Gorp E., ten Cate H.. Infection and inflammation and the coagulation system. Cardiovasc. Res. 2003;60:26–39.
    pubmed: 14522404
  37. So A.K., Varisco P.A., Kemkes-Matthes B., Herkenne-Morard C., Chobaz-Peclat V., Gerster J.C.. Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways. J. Thromb. Haemost. 2003;1:2510–2515.
    pubmed: 14675085
  38. Andreassen S.M., Vinther A.M.L., Nielsen S.S., Andersen P.H., Tnibar A., Kristensen A.T.. Changes in concentrations of haemostatic and inflammatory biomarkers in synovial fluid after intra-articular injection of lipopolysaccharide in horses. BMC Vet. Res. 2017;13:182.
    pmc: PMC5477303pubmed: 28629364
  39. Jacobsen S., Kjelgaard-Hansen M.. Evaluation of a commercially available apparatus for measuring the acute phase protein serum amyloid a in horses. Vet. Rec. 2008;163:327–330.
    pubmed: 18791207
  40. Blom A.M.. The role of complement inhibitors beyond controlling inflammation. J. Intern. Med. 2017;282:116–128.
    pubmed: 28345259
  41. Sakiniene E., Bremell T., Tarkowski A.. Complement depletion aggravates Staphylococcus aureus septicaemia and septic arthritis. Clin. Exp. Immunol. 1999;115:95–102.
    pmc: PMC1905177pubmed: 9933426
  42. Olsson S.E., Reiland S.. The nature of osteochondrosis in animals. Summary and conclusions with comparative aspects on osteochondritis dissecans in man. Acta Radiol. Suppl. 1978;358:299–306.
    pubmed: 233601
  43. Zhang Y., Vasheghani F., Li Y.H., Blati M., Simeone K., Fahmi H.. Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis. Ann. Rheum. Dis. 2015;74:1432–1440.
    pubmed: 24651621
  44. Cejka D., Hayer S., Niederreiter B., Sieghart W., Fuereder T., Zwerina J.. Mammalian target of rapamycin signaling is crucial for joint destruction in experimental arthritis and is activated in osteoclasts from patients with rheumatoid arthritis. Arthritis Rheum. 2010;62:2294–2302.
    pubmed: 20506288
  45. Maicas N., Ferrandiz M.L., Brines R., Ibanez L., Cuadrado A., Koenders M.I.. Deficiency of Nrf2 accelerates the effector phase of arthritis and aggravates joint disease. Antioxid. Redox Signal. 2011;15:889–901.
    pubmed: 21406003
  46. Chiaradia E., Pepe M., Tartaglia M., Scoppetta F., D'Ambrosio C., Renzone G., Avellini L., Moriconi F., Gaiti A., Bertuglia A., Beccati F., Scaloni A.. Gambling on putative biomarkers of osteoarthritis and osteochondrosis by equine synovial fluid proteomics. J. Proteomics. 2012;75(14):4478–4493.
    pubmed: 22361695

Citations

This article has been cited 8 times.
  1. Xiao YP, Cheng YC, Chen C, Xue HM, Yang M, Lin C. Key Common Genes with LTF and MMP9 Between Sepsis and Relapsed B-Cell Lineage Acute Lymphoblastic Leukemia in Children. Biomedicines 2025 Sep 20;13(9).
    doi: 10.3390/biomedicines13092307pubmed: 41007866google scholar: lookup
  2. Secor EJ, Womack SJ, Ysebaert MP, Colville MJ, Reesink HL. Synovial fluid alpha-2-macroglobulin, gelsolin and lubricin distinguish between osteoarthritic and healthy equine joints. Equine Vet J 2026 Jan;58(1):49-59.
    doi: 10.1111/evj.14511pubmed: 40342270google scholar: lookup
  3. Anderson JR, Phelan MM, Caamaño-Gutiérrez E, Clegg PD, Rubio-Martinez LM, Peffers MJ. Metabolomic and proteomic stratification of equine osteoarthritis. Equine Vet J 2025 Sep;57(5):1204-1218.
    doi: 10.1111/evj.14490pubmed: 39972657google scholar: lookup
  4. Bundgaard L, Årman F, Åhrman E, Walters M, Auf dem Keller U, Malmström J, Jacobsen S. An Equine Protein Atlas Highlights Synovial Fluid Proteome Dynamics during Experimentally LPS-Induced Arthritis. J Proteome Res 2024 Nov 1;23(11):4849-4863.
    doi: 10.1021/acs.jproteome.4c00125pubmed: 39395021google scholar: lookup
  5. Blangy-Letheule A, Vergnaud A, Dupas T, Rozec B, Lauzier B, Leroux AA. Spontaneous Sepsis in Adult Horses: From Veterinary to Human Medicine Perspectives. Cells 2023 Mar 30;12(7).
    doi: 10.3390/cells12071052pubmed: 37048125google scholar: lookup
  6. Noordwijk KJ, Qin R, Diaz-Rubio ME, Zhang S, Su J, Mahal LK, Reesink HL. Metabolism and global protein glycosylation are differentially expressed in healthy and osteoarthritic equine carpal synovial fluid. Equine Vet J 2022 Mar;54(2):323-333.
    doi: 10.1111/evj.13440pubmed: 33587757google scholar: lookup
  7. Anderson JR, Phelan MM, Rubio-Martinez LM, Fitzgerald MM, Jones SW, Clegg PD, Peffers MJ. Optimization of Synovial Fluid Collection and Processing for NMR Metabolomics and LC-MS/MS Proteomics. J Proteome Res 2020 Jul 2;19(7):2585-2597.
    doi: 10.1021/acs.jproteome.0c00035pubmed: 32227958google scholar: lookup
  8. Chiaradia E, Pepe M, Orvietani PL, Renzone G, Magini A, Sforna M, Emiliani C, Di Meo A, Scaloni A. Proteome Alterations in Equine Osteochondrotic Chondrocytes. Int J Mol Sci 2019 Dec 7;20(24).
    doi: 10.3390/ijms20246179pubmed: 31817880google scholar: lookup
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