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Equine veterinary journal2021; 54(2); 323-333; doi: 10.1111/evj.13440

Metabolism and global protein glycosylation are differentially expressed in healthy and osteoarthritic equine carpal synovial fluid.

Abstract: Carpal osteochondral fragmentation and subsequent post-traumatic osteoarthritis (PTOA) are leading causes of wastage in the equine athlete. Identification of synovial fluid biomarkers could contribute to the diagnosis and understanding of osteoarthritis (OA) pathophysiology. Objective: The aim of this study was to identify differentially expressed metabolic and glycosylation pathways in synovial fluid from healthy horses and horses with naturally occurring carpal OA. Methods: Cross-sectional, in vivo metabolomics and glycomics study. Methods: In cohort 1, carpal synovial fluid (n = 12 horses; n = 6 healthy, n = 6 OA) was analysed using high-resolution liquid chromatography mass spectrometry (LC-MS). In cohort 2 (n = 40 horses; n = 20 healthy, n = 20 OA), carpal synovial fluid was analysed using lectin microarrays and a lubricin sandwich ELISA. Results: Metabolomic analysis identified >4900 LC-MS features of which 84 identifiable metabolites were differentially expressed (P < .05) between healthy and OA joints, including key pathways related to inflammation (histidine and tryptophan metabolism), oxidative stress (arginine biosynthesis) and collagen metabolism (lysine metabolism). Principle Component Analysis and Partial Least Squares Discriminant Analysis demonstrated separation between healthy and OA synovial fluid. Lectin microarrays identified distinct glycosylation patterns between healthy and OA synovial fluid, including increased Core 1/Core 3 O-glycosylation, increased α-2,3 sialylation and decreased α-1,2 fucosylation in OA. O-glycans predominated over N-glycans in all synovial fluid samples, and synovial fluid lubricin was increased in OA joints as compared to controls. Conclusions: The sample size in cohort 1 was limited, and there is inherent variation in severity and duration of joint injury in naturally occurring OA. However, LC-MS identified up to 5000 unique features. Conclusions: These data suggest new potential diagnostic and therapeutic targets for equine OA. Future targeted metabolomic and glycomic studies should be performed to verify these results. Lectin microarrays could be investigated as a potential screening tool for the diagnosis and therapeutic monitoring of equine OA.
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Publication Date: 2021-03-18 PubMed ID: 33587757PubMed Central: PMC8364562DOI: 10.1111/evj.13440Google Scholar: Lookup
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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 study explores the differences in metabolic and glycosylation pathways in the synovial fluid of healthy horses compared to horses with osteoarthritis focusing on equine athletes. The aim was to uncover potential biomarkers towards improving diagnosis and understanding the disease’s pathophysiology.

Objectives and Methods of the Study

  • The main objective of this study was to identify any differences in metabolism and protein glycosylation in synovial fluid from healthy horses versus those with osteoarthritis (OA).
  • Two cohorts of horses were used for the study. In the first group, 12 horses’ synovial fluid, six healthy and six with OA, was analyzed using high-resolution liquid chromatography mass spectrometry (LC-MS).
  • For the second group, the synovial fluid from 40 horses, 20 healthy and 20 with OA, was examined using lectin microarrays and lubricin sandwich ELISA.

Findings of the Study

  • Metabolomic analysis discovered more than 4900 features, with 84 identifiable and differentially expressed metabolites (changes in their levels) between healthy and OA synovial fluid.
  • This included noticeable changes linked to inflammation (histidine and tryptophan metabolism), oxidative stress (arginine biosynthesis), and collagen metabolism (lysine metabolism).
  • The statistical tests, Principle Component Analysis and Partial Least Squares Discriminant Analysis, showed a clear distinction between healthy and OA synovial fluid samples.
  • The lectin microarray test identified that different protein glycosylation patterns exist between healthy and OA synovial fluid.
  • In particular, in OA synovial fluid, there was an increase in Core 1/Core 3 O-glycosylation and α-2,3 sialylation along with a decrease in α-1,2 fucosylation.
  • O-glycans predominated over N-glycans in all equine synovial fluid samples, and the lubricin levels were found to be increased in the OA joints compared to the healthy ones.

Conclusions and Recommendations

  • The study faced some limitations. The number of equine samples in the first group was limited, and there were also variable severity and duration of joint damage in the case of naturally occurring osteoarthritis.
  • Despite these limitations, new potential diagnostic and therapeutic targets for treating equine OA have been identified.
  • To validate these findings, the authors recommend targeted metabolomic and glycomic studies in future research.
  • The lectin microarray method also holds promise as a potential screening tool to facilitate early diagnosis and therapeutic monitoring of osteoarthritis in equine athletes.

Cite This Article

APA
Noordwijk KJ, Qin R, Diaz-Rubio ME, Zhang S, Su J, Mahal LK, Reesink HL. (2021). Metabolism and global protein glycosylation are differentially expressed in healthy and osteoarthritic equine carpal synovial fluid. Equine Vet J, 54(2), 323-333. https://doi.org/10.1111/evj.13440

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 54
Issue: 2
Pages: 323-333

Researcher Affiliations

Noordwijk, Kira J
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Qin, Rui
  • Department of Chemistry, New York University, New York, NY, USA.
  • Department of Chemistry, University of Alberta, Edmonton, AB, Canada.
Diaz-Rubio, Maria E
  • Proteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, USA.
Zhang, Sheng
  • Proteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, USA.
Su, Jin
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Mahal, Lara K
  • Department of Chemistry, New York University, New York, NY, USA.
  • Department of Chemistry, University of Alberta, Edmonton, AB, Canada.
Reesink, Heidi L
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.

MeSH Terms

  • Animals
  • Biomarkers / metabolism
  • Cross-Sectional Studies
  • Glycosylation
  • Horse Diseases / metabolism
  • Horses
  • Joint Diseases / veterinary
  • Osteoarthritis / metabolism
  • Osteoarthritis / veterinary
  • Synovial Fluid / metabolism

Grant Funding

  • R24 GM08291 / Foundation for the National Institutes of Health
  • R24 GM082910 / NIGMS NIH HHS
  • T32 GM008291 / NIGMS NIH HHS
  • R24 GM08291 / Cornell Veterinary Biobank
  • K08 AR068469 / NIAMS NIH HHS
  • K08AR068469 / NIAMS NIH HHS

Conflict of Interest Statement

CONFLICT OF INTERESTS. No competing interests have been declared.

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Citations

This article has been cited 6 times.
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