Analyze Diet
Equine veterinary journal2025; doi: 10.1111/evj.14490

Metabolomic and proteomic stratification of equine osteoarthritis.

Abstract: Equine osteoarthritis (OA) is predominantly diagnosed through clinical examination and radiography, leading to detection only after significant joint pathology. The pathogenesis of OA remains unclear and while many medications modify the disease's inflammatory components, no curative or reversal treatments exist. Identifying differentially abundant metabolites and proteins correlated with osteoarthritis severity could improve early diagnosis, track disease progression, and evaluate responses to interventions. Objective: To identify molecular markers of osteoarthritis severity based on histological and macroscopic grading. Methods: Cross-sectional study. Methods: Post-mortem synovial fluid was collected from 58 Thoroughbred racehorse joints and 83 joints from mixed breeds. Joints were histologically and macroscopically scored and categorised by OA and synovitis grade. Synovial fluid nuclear magnetic resonance metabolomic and mass spectrometry proteomic analyses were performed, individually and combined. Results: In Thoroughbreds, synovial fluid concentrations of metabolites 2-aminobutyrate, alanine and creatine were elevated for higher OA grades, while glutamate was reduced for both Thoroughbreds and mixed breeds. In mixed breeds, concentrations of three uncharacterised proteins, lipopolysaccharide binding protein and immunoglobulin kappa constant were lower for higher OA grades; concentrations of an uncharacterised protein were higher for OA grade 1 only, and apolipoprotein A1 concentrations were higher for OA grades 1 and 2 compared with lower grades. For Thoroughbreds, gelsolin concentrations were lower for higher OA grades, and afamin was lower at a higher synovitis grade. Correlation analyses of combined metabolomics and proteomics datasets revealed 58 and 32 significant variables for Thoroughbreds and mixed breeds, respectively, with correlations from -0.48 to 0.42 and -0.44 to 0.49. Conclusions: The study's reliance on post-mortem assessments limits correlation with clinical osteoarthritis severity. Conclusions: Following stratification of equine OA severity through histological and macroscopic grading, synovial fluid metabolomic and proteomic profiling identified markers that may support earlier diagnosis and progression tracking. Further research is needed to correlate these markers with clinical osteoarthritis severity.
Publication Date: 2025-02-19 PubMed ID: 39972657DOI: 10.1111/evj.14490Google 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.
  • 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.

The research article focuses on identifying molecular markers of equine osteoarthritis severity through examining post-mortem synovial fluid of Thoroughbred racehorses and mixed breeds. The aim is to enhance early diagnosis, monitor disease progression and gauge responses to medical interventions.

Objective and Methodology:

  • The primary objective of the research was to identify molecular markers that denote the severity of equine osteoarthritis based on histological (microscopic examination of tissues) and macroscopic (visible to the naked eye) grading.
  • The researchers conducted a cross-sectional study involving post-mortem synovial fluid obtained from 58 Thoroughbred racehorse joints and 83 joints from mixed breed horses.
  • The joints were then categorized by osteoarthritis and synovitis grade after being scored both histologically and macroscopically.
  • The synovial fluid was analysed using nuclear magnetic resonance metabolomic and mass spectrometry proteomic analyses, both individually and combined.

Research Findings:

  • In Thoroughbred racehorses, higher osteoarthritis grades were associated with elevated synovial fluid concentrations of metabolites 2-aminobutyrate, alanine, and creatine. Whereas, glutamate concentrations were reduced in both Thoroughbreds and mixed breeds.
  • For mixed breeds, concentrations of three unidentified proteins, a lipopolysaccharide binding protein, and an immunoglobulin kappa constant were lower in higher osteoarthritis grades.
  • Concentrations of a yet to be characterised protein were higher only in osteoarthritis grade 1, and apolipoprotein A1 concentrations were higher in osteoarthritis grades 1 and 2 compared to lower grades.
  • In Thoroughbreds, higher osteoarthritis grades showed lower gelsolin concentrations, and a higher synovitis grade presented lower afamin.
  • The correlation analysis of combined metabolomic and proteomic datasets revealed 58 and 32 significant variables for Thoroughbreds and mixed breeds respectively.

Conclusion:

  • One of the drawbacks of the study is its dependency on post-mortem evaluations, which can limit the correlation with clinical osteoarthritis severity.
  • The article concluded that by stratifying equine osteoarthritis severity through histological and macroscopic grading, it is possible to identify markers within synovial fluid metabolomic and proteomic profiling that may aid in earlier diagnosis and progression tracking.
  • However, more research is essential to link these markers with clinical osteoarthritis severity.

Cite This Article

APA
Anderson JR, Phelan MM, Caamaño-Gutiérrez E, Clegg PD, Rubio-Martinez LM, Peffers MJ. (2025). Metabolomic and proteomic stratification of equine osteoarthritis. Equine Vet J. https://doi.org/10.1111/evj.14490

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Anderson, James R
  • Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
  • Veterinary Anatomy, Physiology and Pathology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
Phelan, Marie M
  • NMR Metabolomics Facility, Liverpool Shared Research Facilities (LivSRF) & Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Liverpool, UK.
Caamaño-Gutiérrez, Eva
  • Computational Biology Facility, Technology Directorate & Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Liverpool, UK.
Clegg, Peter D
  • Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
Rubio-Martinez, Luis M
  • Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
  • Equine Clinical Science, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Neston, UK.
  • Sussex Equine Hospital, West Sussex, UK.
Peffers, Mandy J
  • Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

Grant Funding

  • G1015 / Horse Trust
  • MR/M009114/1 / Medical Research Council
  • 107471/Z/15/Z / Wellcome Trust
  • MR/R502182/1 / Medical Research Council Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing
  • Technology Directorate Voucher (Faculty of Health and Life Sciences, University of Liverpool)

References

This article includes 105 references
  1. Kramer CM, Tsang AS, Koenig T, Jeffcott LB, Dart CM, Dart AJ. Survey of the therapeutic approach and efficacy of pentosan polysulfate for the prevention and treatment of equine osteoarthritis in veterinary practice in Australia.. Aust Vet J 2014;92:482–487.
  2. Truong L‐H, Kuliwaba JS, Tsangari H, Fazzalari NL. Differential gene expression of bone anabolic factors and trabecular bone architectural changes in the proximal femoral shaft of primary hip osteoarthritis patients.. Arthritis Res Ther 2006;8:R188.
  3. Li Y, Xu L, Olsen BR. Lessons from genetic forms of osteoarthritis for the pathogenesis of the disease.. Osteoarthr Cartil 2007;15:1101–1105.
  4. Struglics A, Larsson S, Pratta MA, Kumar S, Lark MW, Lohmander LS. Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase‐ and matrix metalloproteinase‐generated aggrecan fragments.. Osteoarthr Cartil 2006;14:101–113.
  5. Marhardt K, Muurahainen N. Development of a disease‐modifying OA drug (DMOAD) in knee osteoarthritis: the example of sprifermin.. Drug Res 2015;65:S13.
  6. Brommer H, van Weeren PR, Brama PA. New approach for quantitative assessment of articular cartilage degeneration in horses with osteoarthritis.. Am J Vet Res 2003;64:83–87.
  7. 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;17:2735–2743.
  8. Balakrishnan L, Nirujogi RS, Ahmad S, Bhattacharjee M, Manda SS, Renuse S. Proteomic analysis of human osteoarthritis synovial fluid.. Clin Proteomics 2014;11:6.
  9. Taylor SE, Weaver MP, Pitsillides AA, Wheeler BT, Wheeler‐Jones CPD, Shaw DJ. 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;38:502–507.
  10. Zrimsek P, Kadunc Kos V, Mrkun J, Kosec M. Diagnostic value of matrix metalloproteinases 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.
  11. Arai K, Misumi K, Carter SD, Shinbara S, Fujiki M, Sakamoto H. Analysis of cartilage oligomeric matrix protein (COMP) degradation and synthesis in equine joint disease.. Equine Vet J 2005;37:31–36.
  12. Bertuglia A, Pagliara E, Grego E, Ricci A, Brkljaca‐Bottegaro N. Pro‐inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career.. BMC Vet Res 2016;12:246.
  13. Clegg PD, Coughlan AR, Riggs CM, Carter SD. Matrix metalloproteinases 2 and 9 in equine synovial fluids.. Equine Vet J 1997;29:343–348.
  14. Misumi K, Vilim V, Clegg PD, Thompson CCM, Carter SD. Measurement of cartilage oligomeric matrix protein (COMP) in normal and diseased equine synovial fluids.. Osteoarthr Cartil 2001;9:119–127.
  15. Skiöldebrand E, Lorenzo P, Zunino L, Rucklidge GJ, Sandgren B, Carlsten J. Concentration of collagen, aggrecan and cartilage oligomeric matrix protein (COMP) in synovial fluid from equine middle carpal joints.. Equine Vet J 2001;33:394–402.
  16. Yamanokuchi K, Tagami M, Nishimatsu E, Shimizu Y, Hirose Y, Komatsu K. Sandwich ELISA system for cartilage oligomeric matrix protein in equine synovial fluid and serum.. Equine Vet J 2009;41:41–46.
  17. Pinchbeck GL, Clegg PD, Boyde A, Riggs CM. Pathological and clinical features associated with palmar/plantar osteochondral disease of the metacarpo/metatarsophalangeal joint in Thoroughbred racehorses.. Equine Vet J 2013;45:587–592.
  18. Barr ED, Pinchbeck GL, Clegg PD, Boyde A, Riggs CM. Post mortem evaluation of palmar osteochondral disease (traumatic osteochondrosis) of the metacarpo/metatarsophalangeal joint in Thoroughbred racehorses.. Equine Vet J 2009;41:366–371.
  19. Kawcak CE, McIlwraith CW, Norrdin RW, Park RD, Steyn PS. Clinical effects of exercise on subchondral bone of carpal and metacarpophalangeal joints in horses.. Am J Vet Res 2000;61:1252–1258.
  20. Barr ED. The association of bone and cartilage in matrix proteolysis of articular cartilage, and its role in palmar/plantar osteochondral disease in the Thoroughbred racehorse.. PhD thesis. Liverpool, England: University of Liverpool; 2010.
  21. Damyanovich AZ, Staples JR, Chan AD, Marshall KW. Comparative study of normal and osteoarthritic canine synovial fluid using 500 MHz 1H magnetic resonance spectroscopy.. J Orthop Res 1999;17:223–231.
  22. Hugle T, Kovacs H, Heijnen IA, Daikeler T, Baisch U, Hicks JM. Synovial fluid metabolomics in different forms of arthritis assessed by nuclear magnetic resonance spectroscopy.. Clin Exp Rheumatol 2012;30:240–245.
  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;21:85–88.
  24. Mickiewicz B, Heard BJ, Chau JK, Chung M, Hart DA, Shrive NG. Metabolic profiling of synovial fluid in a unilateral ovine model of anterior cruciate ligament reconstruction of the knee suggests biomarkers for early osteoarthritis.. J Orthop Res 2015;33:71–77.
  25. Mickiewicz B, Kelly JJ, Ludwig TE, Weljie AM, Wiley JP, Schmidt TA. Metabolic analysis of knee synovial fluid as a potential diagnostic approach for osteoarthritis.. J Orthop Res 2015;33:1631–1638.
  26. Anderson JR, Chokesuwattanaskul S, Phelan MM, Welting TJM, Lian L‐Y, Peffers MJ. 1H NMR metabolomics identifies underlying inflammatory pathology in osteoarthritis and rheumatoid arthritis synovial joints.. J Proteome Res 2018;17:3780–3790.
  27. Anderson JR, Phelan MM, Foddy L, Clegg PD, Peffers MJ. Ex vivo equine cartilage explant osteoarthritis model: a metabolomics and proteomics study.. J Proteome Res 2020;19(9):3652–3667.
  28. Laus F, Gialletti R, Bazzano M, Laghi L, Dini F, Marchegiani A. Synovial fluid metabolome can differentiate between healthy joints and joints affected by osteoarthritis in horses.. Metabolites 2023;13(8):913.
  29. Svala E, Jin C, Rüetschi U, Ekman S, Lindahl A, Karlsson NG. Characterisation of lubricin in synovial fluid from horses with osteoarthritis.. Equine Vet J 2017;49:116–123.
  30. Skiöldebrand E, Ekman S, Mattsson Hultén L, Svala E, Björkman K, Lindahl A. Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: a new biomarker for the early stages of osteoarthritis.. Equine Vet J 2017;49:662–667.
  31. Peffers MJ, McDermott B, Clegg PD, Riggs CM. Comprehensive protein profiling of synovial fluid in osteoarthritis following protein equalization.. Osteoarthr Cartil 2015;23:1204–1213.
  32. Chiaradia E, Pepe M, Tartaglia M, Scoppetta F, D'Ambrosio C, Renzone G. Gambling on putative biomarkers of osteoarthritis and osteochondrosis by equine synovial fluid proteomics.. J Proteomics 2012;75:4478–4493.
  33. Anderson JR, Smagul A, Simpson D, Clegg PD, Rubio‐Martinez LM, Peffers MJ. The synovial fluid proteome differentiates between septic and nonseptic articular pathologies.. J Proteomics 2019;202:103370.
  34. Timur UT, Jahr H, Anderson J, Green DC, Emans PJ, Smagul A. Identification of tissue‐dependent proteins in knee OA synovial fluid.. Osteoarthr Cartil 2021;29(1):124–133.
  35. Reesink H, Secor E, Womack S, Schayes J. Biomarker discovery using synovial fluid proteomics for equine osteoarthritis.. Osteoarthr Cartil 2023;31:S108.
  36. Roche S, Tiers L, Provansal M, Piva MT, Lehmann S. Interest of major serum protein removal for surface‐enhanced laser desorption/ionization–time of flight (SELDI‐TOF) proteomic blood profiling.. Proteome Sci 2006;4:20.
  37. Puangpila C, Mayadunne E, El Rassi Z. Liquid phase based separation systems for depletion, prefractionation, and enrichment of proteins in biological fluids and matrices for in‐depth proteomics analysis—an update covering the period 2011–2014.. Electrophoresis 2015;36:238–252.
  38. Fonslow BR, Carvalho PC, Academia K, Freeby S, Xu T, Nakorchevsky A. Improvements in proteomic metrics of low abundance proteins through proteome equalization using ProteoMiner prior to MudPIT.. J Proteome Res 2011;10:3690–3700.
  39. Furka A, Sebestyen F, Asgedom M, Dibo G. General method for rapid synthesis of multicomponent peptide mixtures.. Int J Pept Protein Res 1991;37:487–493.
  40. Lam KS, Salmon SE, Hersh EM, Hruby VJ, Kazmierski WM, Knapp RJ. A new type of synthetic peptide library for identifying ligand‐binding activity.. Nature 1991;354:82–84.
  41. Peffers MJ, Thornton DJ, Clegg PD. Characterization of neopeptides in equine articular cartilage degradation.. J Orthop Res 2016;34:106–120.
  42. Polur I, Lee PL, Servais JM, Xu L, Li Y. Role of HTRA1, a serine protease, in the progression of articular cartilage degeneration.. Histol Histopathol 2010;25:599–608.
  43. Ben‐Aderet L, Merquiol E, Fahham D, Kumar A, Reich E, Ben‐Nun Y. Detecting cathepsin activity in human osteoarthritis via activity‐based probes.. Arthritis Res Ther 2015;17:69.
  44. Peffers MJ, Cillero‐Pastor B, Eijkel GB, Clegg PD, Heeren RM. Matrix assisted laser desorption ionization mass spectrometry imaging identifies markers of ageing and osteoarthritic cartilage.. Arthritis Res Ther 2014;16:R110.
  45. Miller RE, Ishihara S, Tran PB, Golub SB, Last K, Miller RJ. An aggrecan fragment drives osteoarthritis pain through Toll‐like receptor 2.. JCI Insight 2018;3:1–9.
  46. Anderson JR, Phelan MM, Rubio‐Martinez LM, Fitzgerald MM, Jones SW, Clegg PD. Optimization of synovial fluid collection and processing for NMR metabolomics and LC‐MS/MS proteomics.. J Proteome Res 2020;19:2585–2597.
  47. Cavill R, Jennen D, Kleinjans J, Briedé JJ. Transcriptomic and metabolomic data integration.. Brief Bioinform 2016;17:891–901.
  48. McIlwraith CW, Frisbie DD, Kawcak CE, Fuller CJ, Hurtig M, Cruz A. The OARSI histopathology initiative—recommendations for histological assessments of osteoarthritis in the horse.. Osteoarthr Cartil 2010;18:S93–S105.
  49. Little CB, Smith MM, Cake MA, Read RA, Murphy MJ, Barry FP. The OARSI histopathology initiative—recommendations for histological assessments of osteoarthritis in sheep and goats.. Osteoarthr Cartil 2010;18:S80–S92.
  50. Krenn V, Morawietz L, Burmester G‐R, Kinne RW, Mueller‐Ladner U, Muller B. Synovitis score: discrimination between chronic low‐grade and high‐grade synovitis.. Histopathol 2006;49:358–364.
  51. McHugh ML. Interrater reliability: the kappa statistic.. Biochem Med Zagreb 2012;22:276–282.
  52. Pedregosa F, Varoquaux G, Gramfort A, Michel V, Thirion B, Grisel O. Scikit‐learn: machine learning in python.. J Mach Learn Res 2011;12:2825–2830.
  53. Pearson K. Mathematical contributions to the theory of evolution. X. Supplement to a memoir on skew variation.. Phil Trans R Soc Lond A 1901;197:443–459.
    doi: 10.1098/rsta.1901.0023google scholar: lookup
  54. Anderson JR, Jensen A. Study design synopsis: ‘omics’ terminologies—a guide for the equine clinician.. Equine Vet J 2025;57(1):19–27.
    doi: 10.1111/evj.14404google scholar: lookup
  55. Sumner LW, Amberg A, Barrett D, Beale MH, Beger R, Daykin CA. Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI).. Metabolomics 2007;3:211–221.
  56. Haug K, Cochrane K, Nainala VC, Williams M, Chang J, Jayaseelan KV. MetaboLights: a resource evolving in response to the needs of its scientific community.. Nucleic Acids Res 2019;48(D1):D440–D444.
  57. 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 Proteomics 2012;75:2869–2878.
  58. Perez‐Riverol Y, Csordas A, Bai J, Bernal‐Llinares M, Hewapathirana S, Kundu DJ. The PRIDE database and related tools and resources in 2019: improving support for quantification data.. Nucleic Acids Res 2019;47:D442–D450.
  59. Peffers M, Jones AR, McCabe A, Anderson J. Neopeptide analyser: a software tool for neopeptide discovery in proteomics data.. Wellcome Open Res 2017;2:24.
  60. Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods.. Biostatistics 2007;8:118–127.
  61. Worley B, Powers R. Multivariate analysis in metabolomics.. Curr Metabolomics 2013;1:92–107.
  62. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing.. J R Stat Soc Ser B Stat Methodol 1995;57:289–300.
  63. Kohl SM, Klein MS, Hochrein J, Oefner PJ, Spang R, Gronwald W. State‐of‐the art data normalization methods improve NMR‐based metabolomic analysis.. Metabolomics 2012;8:146–160.
  64. Team_R_Core. R: a language and environment for statistical computing.. Vienna, Austria: R Foundation for Statistical Computing; 2019.
  65. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool.. J Mol Biol 1990;215:403–410.
  66. Luo Q, Qin X, Qiu Y, Hou L, Yang N. The change of synovial fluid proteome in rabbit surgery‐induced model of knee osteoarthritis.. Am J Transl Res 2018;10:2087–2101.
  67. Cooke TD, Hurd ER, Jasin HE, Bienenstock J, Ziff M. Identification of immunoglobulins and complement in rheumatoid articular collagenous tissues.. Arthritis Rheum 1975;18:541–551.
  68. Lawrence D, Bao S, Canfield PJ, Allanson M, Husband AJ. Elevation of immunoglobulin deposition in the synovial membrane of dogs with cranial cruciate ligament rupture.. Vet Immunol Immunopathol 1998;65:89–96.
  69. Wen Z‐H, Chang Y‐C, Jean Y‐H. Excitatory amino acid glutamate: role in peripheral nociceptive transduction and inflammation in experimental and clinical osteoarthritis.. Osteoarthr Cartil 2015;23:2009–2016.
  70. Piepoli T, Mennuni L, Zerbi S, Lanza M, Rovati LC, Caselli G. Glutamate signaling in chondrocytes and the potential involvement of NMDA receptors in cell proliferation and inflammatory gene expression.. Osteoarthr Cartil 2009;17:1076–1083.
  71. McNearney T, Speegle D, Lawand N, Lisse J, Westlund KN. Excitatory amino acid profiles of synovial fluid from patients with arthritis.. J Rheumatol 2000;27:739–745.
  72. Lawand NB, McNearney T, Westlund KN. Amino acid release into the knee joint: key role in nociception and inflammation.. Pain 2000;86:69–74.
  73. Jean Y‐H, Wen Z‐H, Chang Y‐C, Huang G‐S, Lee H‐S, Hsieh S‐P. Increased concentrations of neuro‐excitatory amino acids in rat anterior cruciate ligament‐transected knee joint dialysates: a microdialysis study.. J Orthop Res 2005;23:569–575.
  74. Shet K, Siddiqui SM, Yoshihara H, Kurhanewicz J, Ries M, Li X. High‐resolution magic angle spinning NMR spectroscopy of human osteoarthritic cartilage.. NMR Biomed 2012;25:538–544.
  75. Huster D, Schiller J, Naji L, Kaufmann J, Arnold K. NMR studies of cartilage—dynamics, diffusion, degradation.. Berlin, Heidelberg: Springer; 2004. p. 465–503.
  76. Yin HL, Kwiatkowski DJ, Mole JE, Cole FS. Structure and biosynthesis of cytoplasmic and secreted variants of gelsolin.. J Biol Chem 1984;259:5271–5276.
  77. Kaneva MK, Greco KV, Headland SE, Montero‐Melendez T, Mori P, Greenslade K. Identification of novel chondroprotective mediators in resolving inflammatory exudates.. J Immunol 2017;198:2876–2885s.
  78. Piktel E, Levental I, Durnaś B, Janmey P, Bucki R, Piktel E. Plasma gelsolin: indicator of inflammation and its potential as a diagnostic tool and therapeutic target.. Int J Mol Sci 2018;19:2516.
  79. DiNubile MJ, Stossel TP, Ljunghusen OC, Ferrara JLM, Antin JH. Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantation.. Blood 2002;100:4367–4371.
  80. Ito H, Kambe H, Kimura Y, Nakamura H, Hayashi E, Kishimoto T. Depression of plasma gelsolin level during acute liver injury.. Gastroenterology 1992;102:1686–1692.
  81. Osborn TM, Verdrengh M, Stossel TP, Tarkowski A, Bokarewa M. Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis.. Arthritis Res Ther 2008;10:R117.
  82. Aidinis V, Carninci P, Armaka M, Witke W, Harokopos V, Pavelka N. Cytoskeletal rearrangements in synovial fibroblasts as a novel pathophysiological determinant of modeled rheumatoid arthritis.. PLoS Genet 2005;1:455–466.
  83. Gupta AK, Parasar D, Sagar A, Choudhary V, Chopra BS, Garg R. Analgesic and anti‐inflammatory properties of gelsolin in acetic acid induced writhing, tail immersion and carrageenan induced paw edema in mice.. PLoS One 2015;10:e0135558.
  84. Peffers MJ, Riasat K, Boyer L, Bailey H, Cywińska A, Przewozny M. Gelsolin and lipoprotein binding protein within synovial fluid as diagnostic markers of equine osteoarthritis.. Equine Vet J 2024;56:11–12.
  85. Ranoa DRE, Kelley SL, Tapping RI. Human lipopolysaccharide‐binding protein (LBP) and CD14 independently deliver triacylated lipoproteins to toll‐like receptor 1 (TLR1) and TLR2 and enhance formation of the ternary signaling complex.. J Biol Chem 2013;288:9729–9741.
  86. Citronberg JS, Wilkens LR, Lim U, Hullar MAJ, White E, Newcomb PA. Reliability of plasma lipopolysaccharide‐binding protein (LBP) from repeated measures in healthy adults.. Cancer Causes Control 2016;27:1163–1166.
  87. Heumann D, Bas S, Gallay P, Le Roy D, Barras C, Mensi N. Lipopolysaccharide binding protein as a marker of inflammation in synovial fluid of patients with arthritis: correlation with interleukin 6 and C‐reactive protein.. J Rheumatol 1995;22:1224–1229.
  88. Huang ZY, Perry E, Huebner JL, Katz B, Li Y‐J, Kraus VB. Biomarkers of inflammation—LBP and TLR‐ predict progression of knee osteoarthritis in the DOXY clinical trial.. Osteoarthr Cartil 2018;26(12):1658–1665.
  89. Lamping N, Dettmer R, Schröder NW, Pfeil D, Hallatschek W, Burger R. LPS‐binding protein protects mice from septic shock caused by LPS or gram‐negative bacteria.. J Clin Invest 1998;101:2065–2071.
  90. Schumann RR, Rietschel ET, Loppnow H. The role of CD14 and lipopolysaccharide‐binding protein (LBP) in the activation of different cell types by endotoxin.. Med Microbiol Immunol 1994;183:279–297.
  91. Wojdasiewicz P, Poniatowski ŁA, Szukiewicz D. The role of inflammatory and anti‐inflammatory cytokines in the pathogenesis of osteoarthritis.. Mediators Inflamm 2014;2014:561459.
  92. Shahid M. Investigations on the quantitative and qualitative protein content in serum and synovial fluid of dogs with osteoarthritis.. PhD thesis. Berlin, Germany: Free University of Berlin; 2018.
  93. Luc G, Majd Z, Poulain P, Elkhalil L, Fruchart JC. Interstitial fluid apolipoprotein A‐II: an association with the occurrence of myocardial infarction.. Atherosclerosis 1996;127:131–137.
  94. Ramella NA, Andújar I, Ríos JL, Rosú SA, Tricerri MA, Schinella GR. Human apolipoprotein A‐I Gly26Arg stimulation of inflammatory responses via NF‐kB activation: potential roles in amyloidosis?. Pathophysiology 2018;25(4):397–404.
  95. Silver DL, Wang N, Xiao X, Tall AR. High density lipoprotein (HDL) particle uptake mediated by scavenger receptor class B type 1 results in selective sorting of HDL cholesterol from protein and polarized cholesterol secretion.. J Biol Chem 2001;276:25287–25293.
  96. Rader DJ. Regulation of reverse cholesterol transport and clinical implications.. Am J Cardiol 2003;92:42J–49J.
  97. de Seny D, Cobraiville G, Charlier E, Neuville S, Lutteri L, Le Goff C. Apolipoprotein‐A1 as a damage‐associated molecular patterns protein in osteoarthritis: ex vivo and in vitro pro‐inflammatory properties.. PLoS One 2015;10:e0122904.
  98. Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: current understanding with therapeutic implications.. Arthritis Res Ther 2017;19:18.
  99. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!).. Osteoarthr Cartil 2013;21:16–21.
  100. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.. Nat Rev Rheumatol 2010;6:625–635.
  101. Ritter SY, Collins J, Krastins B, Sarracino D, Lopez M, Losina E. Mass spectrometry assays of plasma biomarkers to predict radiographic progression of knee osteoarthritis.. Arthritis Res Ther 2014;16:456.
  102. Dieplinger H, Dieplinger B. Afamin—a pleiotropic glycoprotein involved in various disease states.. Clin Chim Acta 2015;446:105–110.
  103. Mihara E, Hirai H, Yamamoto H, Tamura‐Kawakami K, Matano M, Kikuchi A. Active and water‐soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α‐albumin.. Elife 2016;5:e11621.
  104. Zhou Y, Wang T, Hamilton JL, Chen D. Wnt/β‐catenin signaling in osteoarthritis and in other forms of arthritis.. Curr Rheumatol Rep 2017;19:53.
  105. Salek RM, Steinbeck C, Viant MR, Goodacre R, Dunn WB. The role of reporting standards for metabolite annotation and identification in metabolomic studies.. Gigascience 2013;2:13.

Citations

This article has been cited 0 times.