FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Metabolites / Synovial Fluid Metabolome Can Differentiate between Healthy ...
Metabolites2023; 13(8); 913; doi: 10.3390/metabo13080913

Synovial Fluid Metabolome Can Differentiate between Healthy Joints and Joints Affected by Osteoarthritis in Horses.

Abstract: Osteoarthritis (OA) is a common cause of lameness in sport horses with a significant economic impact. The prevention of OA is crucial since no effective treatment is available. This study aimed to apply untargeted metabolomic analysis to investigate the differences in synovial fluid (SF) composition between healthy and OA-affected joints in horses. SF collected from healthy (n.8) and OA (n.11) horses was analyzed using H-NMR analysis. Metabolomic analysis allowed 55 different metabolites to be identified and quantified in SF samples. Nineteen metabolites were found to be differently concentrated in OA compared to control horses. Synovial fluids from the OC group were found to be higher in 1,3-dihydroxyacetone but lower in tryptophan, phenylalanine, tyrosine, uridine, creatinine, creatine, glycine, choline, asparagine, glutamine, arginine, 3-hydroxybutyrate, valine, 2-hydroxyisovalerate, α-ketoisovaleric acid, 3-methyl-2-oxovalerate, 3-hydroxyisobutyrate, isoleucine, and methionine compared to the controls. A variety of SF metabolites significantly changed following joint disease, demonstrating the complex mechanism underlying osteoarthritis in horses and highlighting the value of applying the metabolomic approach in clinical research.
Get Full Text
Publication Date: 2023-08-04 PubMed ID: 37623857PubMed Central: PMC10456394DOI: 10.3390/metabo13080913Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

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 article reveals the differences in synovial fluid (liquid that lubricates joints) compositions in healthy horses versus those affected by Osteoarthritis (OA), a common cause of lameness, using untargeted metabolomic analysis.

Methodology

  • The study involved the collection and analysis of synovial fluid samples from 8 horses without OA and 11 horses with OA.
  • The analysis involved the usage of a technique called H-NMR (Proton Nuclear Magnetic Resonance) spectroscopy, which is capable of identifying and quantifying numerous metabolites in the synovial fluid.
  • A total of 55 different metabolites were identified in the study.

Key Findings

  • The analysis revealed that there were significant differences in the concentration of 19 different metabolites between the OA horses and the control horses.
  • Notably, synovial fluid from the OA-affected horses had higher levels of 1,3-dihydroxyacetone, a metabolite involved in energy metabolism.
  • However, the same OA-affected horses had lower levels of a variety of other metabolites, including several amino acids like tryptophan, phenylalanine, and tyrosine, as well as other metabolites involved in energy metabolism like creatinine, creatine, and 3-hydroxybutyrate.

Implications

  • The study showcases the metabolomic approach’s value in clinical research, particularly in understanding the changes in synovial fluid composition related to joint diseases like osteoarthritis.
  • These changes in metabolite levels might reflect the changes in metabolic processes occurring in OA-affected joints versus healthy joints, offering insights into the complex mechanism underlying horse osteoarthritis.
  • The marked differences in metabolite concentrations between OA and non-OA horses might provide markers for early detection or progression of osteoarthritis, aiding in timely and effective prevention strategies, given the lack of effective treatments for OA.

Cite This Article

APA
Laus F, Gialletti R, Bazzano M, Laghi L, Dini F, Marchegiani A. (2023). Synovial Fluid Metabolome Can Differentiate between Healthy Joints and Joints Affected by Osteoarthritis in Horses. Metabolites, 13(8), 913. https://doi.org/10.3390/metabo13080913

Publication

Metabolites
ISSN: 2218-1989
NlmUniqueID: 101578790
Country: Switzerland
Language: English
Volume: 13
Issue: 8
PII: 913

Researcher Affiliations

Laus, Fulvio
  • School of Biosciences and Veterinary Medicine, University of Camerino, 62024 Macerata, Italy.
Gialletti, Rodolfo
  • Department of Veterinary Medicine, University of Perugia, 06123 Perugia, Italy.
Bazzano, Marilena
  • School of Biosciences and Veterinary Medicine, University of Camerino, 62024 Macerata, Italy.
Laghi, Luca
  • Centre of Foodomics, Department of Agro-Food Science and Technology, University of Bologna, 40100 Bologna, Italy.
Dini, Fabrizio
  • School of Biosciences and Veterinary Medicine, University of Camerino, 62024 Macerata, Italy.
Marchegiani, Andrea
  • School of Biosciences and Veterinary Medicine, University of Camerino, 62024 Macerata, Italy.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 48 references
  1. Labens R., Schramme M.C., Barr A.R. Equine Medicine, Surgery and Reproduction. Saunders/Elsevier; Edinburgh, Scotland: 2013. Orthopaedics 1: Diagnosis of Lameness; pp. 309–328.
  2. Anderson JR, Phelan MM, Clegg PD, Peffers MJ, Rubio-Martinez LM. Synovial Fluid Metabolites Differentiate between Septic and Nonseptic Joint Pathologies.. J Proteome Res 2018 Aug 3;17(8):2735-2743.
    doi: 10.1021/acs.jproteome.8b00190pmc: PMC6092013pubmed: 29969035google scholar: lookup
  3. Menarim BC, Gillis KH, Oliver A, Ngo Y, Werre SR, Barrett SH, Rodgerson DH, Dahlgren LA. Macrophage Activation in the Synovium of Healthy and Osteoarthritic Equine Joints.. Front Vet Sci 2020;7:568756.
    doi: 10.3389/fvets.2020.568756pmc: PMC7726135pubmed: 33324696google scholar: lookup
  4. 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
  5. Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis.. Ann N Y Acad Sci 2010 Mar;1192:230-7.
    doi: 10.1111/j.1749-6632.2009.05240.xpubmed: 20392241google scholar: lookup
  6. Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases.. Animals (Basel) 2021 Jan 19;11(1).
    doi: 10.3390/ani11010234pmc: PMC7832834pubmed: 33477808google scholar: lookup
  7. Taylor SE, Weaver MP, Pitsillides AA, Wheeler BT, Wheeler-Jones CP, Shaw DJ, Smith RK. Cartilage oligomeric matrix protein and hyaluronan levels in synovial fluid from horses with osteoarthritis of the tarsometatarsal joint compared to a control population.. Equine Vet J 2006 Nov;38(6):502-7.
    doi: 10.2746/042516406X156073pubmed: 17124839google scholar: lookup
  8. Zrimšek P, Kadunc Kos V, Mrkun J, Kosec M. Diagnostic Value of MMP-2 and MMP-9 in Synovial Fluid for Identifying Osteoarthritis in the Distal Interphalangeal Joint in Horses. Acta Vet. Brno 2007;76:87–95.
    doi: 10.2754/avb200776010087google scholar: lookup
  9. Desjardin C, Riviere J, Vaiman A, Morgenthaler C, Diribarne M, Zivy M, Robert C, Le Moyec L, Wimel L, Lepage O, Jacques C, Cribiu E, Schibler L. Omics technologies provide new insights into the molecular physiopathology of equine osteochondrosis.. BMC Genomics 2014 Oct 31;15(1):947.
    doi: 10.1186/1471-2164-15-947pmc: PMC4233069pubmed: 25359417google scholar: lookup
  10. Nelson B.B., Goodrich L.R. Robinson’s Current Therapy in Equine Medicine. 7th ed. Elsevier; Amsterdam, The Netherlands: 2015. Treatment of Joint Disease; pp. 798–804.
    doi: 10.1016/B978-1-4557-4555-5.00187-4google scholar: lookup
  11. Billinghurst R.C. Current Therapy in Equine Medicine. 5th ed. Elsevier; Amsterdam, The Netherlands: 2003. Biomarkers of Joint Disease; pp. 513–520.
    doi: 10.1016/B978-0-7216-9540-2.50156-0google scholar: lookup
  12. Bujak R, Struck-Lewicka W, Markuszewski MJ, Kaliszan R. Metabolomics for laboratory diagnostics.. J Pharm Biomed Anal 2015 Sep 10;113:108-20.
    doi: 10.1016/j.jpba.2014.12.017pubmed: 25577715google scholar: lookup
  13. Madsen R, Lundstedt T, Trygg J. Chemometrics in metabolomics--a review in human disease diagnosis.. Anal Chim Acta 2010 Feb 5;659(1-2):23-33.
    doi: 10.1016/j.aca.2009.11.042pubmed: 20103103google scholar: lookup
  14. Ruiz-Romero C, Blanco FJ. Proteomics role in the search for improved diagnosis, prognosis and treatment of osteoarthritis.. Osteoarthritis Cartilage 2010 Apr;18(4):500-9.
    doi: 10.1016/j.joca.2009.11.012pubmed: 20060947google scholar: lookup
  15. Mateos J, Lourido L, Fernández-Puente P, Calamia V, Fernández-López C, Oreiro N, Ruiz-Romero C, Blanco FJ. Differential protein profiling of synovial fluid from rheumatoid arthritis and osteoarthritis patients using LC-MALDI TOF/TOF.. J Proteomics 2012 Jun 6;75(10):2869-78.
    doi: 10.1016/j.jprot.2011.12.042pubmed: 22245418google scholar: lookup
  16. Haralambus R, Florczyk A, Sigl E, Gültekin S, Vogl C, Brandt S, Schnierer M, Gamerith C, Jenner F. Detection of synovial sepsis in horses using enzymes as biomarkers.. Equine Vet J 2022 May;54(3):513-522.
    doi: 10.1111/evj.13459pmc: PMC9290786pubmed: 33977535google scholar: lookup
  17. Lineham B, Altaie A, Harwood P, McGonagle D, Pandit H, Jones E. A systematic review on the potential value of synovial fluid biomarkers to predict clinical outcomes in cartilage repair treatments.. Osteoarthritis Cartilage 2022 Aug;30(8):1035-1049.
    doi: 10.1016/j.joca.2022.05.007pubmed: 35618204google scholar: lookup
  18. 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.13440pmc: PMC8364562pubmed: 33587757google scholar: lookup
  19. Laghi L, Picone G, Capozzi F. Nuclear Magnetic Resonance for Foodomics beyond Food Analysis. Trends Anal. Chem. 2014;59:93–102.
    doi: 10.1016/j.trac.2014.04.009google scholar: lookup
  20. de Grauw JC, van de Lest CH, van Weeren PR. A targeted lipidomics approach to the study of eicosanoid release in synovial joints.. Arthritis Res Ther 2011 Jul 27;13(4):R123.
    doi: 10.1186/ar3427pmc: PMC3239362pubmed: 21794148google scholar: lookup
  21. Kosinska MK, Eichner G, Schmitz G, Liebisch G, Steinmeyer J. A comparative study on the lipidome of normal knee synovial fluid from humans and horses.. PLoS One 2021;16(4):e0250146.
    doi: 10.1371/journal.pone.0250146pmc: PMC8051782pubmed: 33861772google scholar: lookup
  22. Graham RJTY, Anderson JR, Phelan MM, Cillan-Garcia E, Bladon BM, Taylor SE. Metabolomic analysis of synovial fluid from Thoroughbred racehorses diagnosed with palmar osteochondral disease using magnetic resonance imaging.. Equine Vet J 2020 May;52(3):384-390.
    doi: 10.1111/evj.13199pubmed: 31657070google scholar: lookup
  23. Lacitignola L, Fanizzi FP, Francioso E, Crovace A. 1H NMR investigation of normal and osteo-arthritic synovial fluid in the horse.. Vet Comp Orthop Traumatol 2008;21(1):85-8.
    doi: 10.3415/VCOT-06-12-0101pubmed: 18288348google scholar: lookup
  24. Robinson CS, Singer ER, Piviani M, Rubio-Martinez LM. Are serum amyloid A or D-lactate useful to diagnose synovial contamination or sepsis in horses?. Vet Rec 2017 Oct 21;181(16):425.
    doi: 10.1136/vr.104386pmc: PMC5738594pubmed: 28765498google scholar: lookup
  25. Brugaletta G, De Cesare A, Laghi L, Manfreda G, Zampiga M, Oliveri C, Pérez-Calvo E, Litta G, Lolli S, Sirri F. A multi-omics approach to elucidate the mechanisms of action of a dietary muramidase administered to broiler chickens.. Sci Rep 2022 Apr 1;12(1):5559.
    doi: 10.1038/s41598-022-09546-6pmc: PMC8976025pubmed: 35365750google scholar: lookup
  26. R: The R Project for Statistical Computing. [(accessed on 22 June 2023)]. Available online: https://www.r-project.org/
  27. Wishart DS, Tzur D, Knox C, Eisner R, Guo AC, Young N, Cheng D, Jewell K, Arndt D, Sawhney S, Fung C, Nikolai L, Lewis M, Coutouly MA, Forsythe I, Tang P, Shrivastava S, Jeroncic K, Stothard P, Amegbey G, Block D, Hau DD, Wagner J, Miniaci J, Clements M, Gebremedhin M, Guo N, Zhang Y, Duggan GE, Macinnis GD, Weljie AM, Dowlatabadi R, Bamforth F, Clive D, Greiner R, Li L, Marrie T, Sykes BD, Vogel HJ, Querengesser L. HMDB: the Human Metabolome Database.. Nucleic Acids Res 2007 Jan;35(Database issue):D521-6.
    doi: 10.1093/nar/gkl923pmc: PMC1899095pubmed: 17202168google scholar: lookup
  28. Box GEP, Cox DR. An Analysis of Transformations. J. R. Stat. Society. Ser. B 1964;26:211–252.
    doi: 10.1111/j.2517-6161.1964.tb00553.xgoogle scholar: lookup
  29. Parada-Turska J, Zgrajka W, Majdan M. Kynurenic acid in synovial fluid and serum of patients with rheumatoid arthritis, spondyloarthropathy, and osteoarthritis.. J Rheumatol 2013 Jun;40(6):903-9.
    doi: 10.3899/jrheum.121035pubmed: 23588943google scholar: lookup
  30. Kang KY, Lee SH, Jung SM, Park SH, Jung BH, Ju JH. Downregulation of Tryptophan-related Metabolomic Profile in Rheumatoid Arthritis Synovial Fluid.. J Rheumatol 2015 Nov;42(11):2003-11.
    doi: 10.3899/jrheum.141505pubmed: 26329338google scholar: lookup
  31. Nowicka-Stążka P, Langner E, Turski W, Rzeski W, Parada-Turska J. Quinaldic acid in synovial fluid of patients with rheumatoid arthritis and osteoarthritis and its effect on synoviocytes in vitro.. Pharmacol Rep 2018 Apr;70(2):277-283.
    doi: 10.1016/j.pharep.2017.09.010pubmed: 29477035google scholar: lookup
  32. Li J, Che N, Xu L, Zhang Q, Wang Q, Tan W, Zhang M. LC-MS-based serum metabolomics reveals a distinctive signature in patients with rheumatoid arthritis.. Clin Rheumatol 2018 Jun;37(6):1493-1502.
    doi: 10.1007/s10067-018-4021-6pubmed: 29442259google scholar: lookup
  33. Dai M, Sui B, Xue Y, Liu X, Sun J. Cartilage repair in degenerative osteoarthritis mediated by squid type II collagen via immunomodulating activation of M2 macrophages, inhibiting apoptosis and hypertrophy of chondrocytes.. Biomaterials 2018 Oct;180:91-103.
    doi: 10.1016/j.biomaterials.2018.07.011pubmed: 30031224google scholar: lookup
  34. Deng L, Yao P, Li L, Ji F, Zhao S, Xu C, Lan X, Jiang P. p53-mediated control of aspartate-asparagine homeostasis dictates LKB1 activity and modulates cell survival.. Nat Commun 2020 Apr 9;11(1):1755.
    doi: 10.1038/s41467-020-15573-6pmc: PMC7145870pubmed: 32273511google scholar: lookup
  35. Kim H. Glutamine as an immunonutrient.. Yonsei Med J 2011 Nov;52(6):892-7.
    doi: 10.3349/ymj.2011.52.6.892pmc: PMC3220259pubmed: 22028151google scholar: lookup
  36. Takahashi S, Saegusa J, Sendo S, Okano T, Akashi K, Irino Y, Morinobu A. Glutaminase 1 plays a key role in the cell growth of fibroblast-like synoviocytes in rheumatoid arthritis.. Arthritis Res Ther 2017 Apr 11;19(1):76.
    doi: 10.1186/s13075-017-1283-3pmc: PMC5387190pubmed: 28399896google scholar: lookup
  37. McNeal CJ, Meininger CJ, Reddy D, Wilborn CD, Wu G. Safety and Effectiveness of Arginine in Adults.. J Nutr 2016 Dec;146(12):2587S-2593S.
    doi: 10.3945/jn.116.234740pubmed: 27934649google scholar: lookup
  38. Carlson AK, Rawle RA, Wallace CW, Adams E, Greenwood MC, Bothner B, June RK. Global metabolomic profiling of human synovial fluid for rheumatoid arthritis biomarkers.. Clin Exp Rheumatol 2019 May-Jun;37(3):393-399.
    pubmed: 30620276
  39. Aledo JC. Methionine in proteins: The Cinderella of the proteinogenic amino acids.. Protein Sci 2019 Oct;28(10):1785-1796.
    doi: 10.1002/pro.3698pmc: PMC6739822pubmed: 31359525google scholar: lookup
  40. Li C, Chen B, Fang Z, Leng YF, Wang DW, Chen FQ, Xu X, Sun ZL. Metabolomics in the development and progression of rheumatoid arthritis: A systematic review.. Joint Bone Spine 2020 Oct;87(5):425-430.
    doi: 10.1016/j.jbspin.2020.05.005pubmed: 32473419google scholar: lookup
  41. Liu J, Shikhman AR, Lotz MK, Wong CH. Hexosaminidase inhibitors as new drug candidates for the therapy of osteoarthritis.. Chem Biol 2001 Jul;8(7):701-11.
    doi: 10.1016/S1074-5521(01)00045-Xpubmed: 11451670google scholar: lookup
  42. Shikhman AR, Brinson DC, Lotz M. Profile of glycosaminoglycan-degrading glycosidases and glycoside sulfatases secreted by human articular chondrocytes in homeostasis and inflammation.. Arthritis Rheum 2000 Jun;43(6):1307-14.
    doi: 10.1002/1529-0131(200006)43:6<1307::AID-ANR13>3.0.CO;2-3pubmed: 10857789google scholar: lookup
  43. Chenna Narendra S, Chalise JP, Magnusson M, Uppugunduri S. Local but Not Systemic Administration of Uridine Prevents Development of Antigen-Induced Arthritis.. PLoS One 2015;10(10):e0141863.
    doi: 10.1371/journal.pone.0141863pmc: PMC4625961pubmed: 26512984google scholar: lookup
  44. Anderson JR, Chokesuwattanaskul S, Phelan MM, Welting TJM, Lian LY, Peffers MJ, Wright HL. (1)H NMR Metabolomics Identifies Underlying Inflammatory Pathology in Osteoarthritis and Rheumatoid Arthritis Synovial Joints.. J Proteome Res 2018 Nov 2;17(11):3780-3790.
    doi: 10.1021/acs.jproteome.8b00455pmc: PMC6220363pubmed: 30229649google scholar: lookup
  45. Adams SB Jr, Setton LA, Kensicki E, Bolognesi MP, Toth AP, Nettles DL. Global metabolic profiling of human osteoarthritic synovium.. Osteoarthritis Cartilage 2012 Jan;20(1):64-7.
    doi: 10.1016/j.joca.2011.10.010pmc: PMC3254801pubmed: 22063369google scholar: lookup
  46. Zhai G, Wang-Sattler R, Hart DJ, Arden NK, Hakim AJ, Illig T, Spector TD. Serum branched-chain amino acid to histidine ratio: a novel metabolomic biomarker of knee osteoarthritis.. Ann Rheum Dis 2010 Jun;69(6):1227-31.
    doi: 10.1136/ard.2009.120857pubmed: 20388742google scholar: lookup
  47. Hosea Blewett HJ. Exploring the mechanisms behind S-adenosylmethionine (SAMe) in the treatment of osteoarthritis.. Crit Rev Food Sci Nutr 2008 May;48(5):458-63.
    doi: 10.1080/10408390701429526pubmed: 18464034google scholar: lookup
  48. Lauwers M, Courties A, Sellam J, Wen C. The cholinergic system in joint health and osteoarthritis: a narrative-review.. Osteoarthritis Cartilage 2021 May;29(5):643-653.
    doi: 10.1016/j.joca.2021.02.005pubmed: 33609692google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,359 horse owners like you who receive our email updates on horse health and nutrition.