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Journal of orthopaedic research : official publication of the Orthopaedic Research Society2021; 40(3); 595-603; doi: 10.1002/jor.25075

Gene expression analysis of subchondral bone, cartilage, and synovium in naturally occurring equine palmar/plantar osteochondral disease.

Abstract: Osteoarthritis (OA) is a disease of the entire joint but the relationship between pathological events in various joint tissues is poorly understood. We examined concurrent changes in bone, cartilage, and synovium in a naturally occurring equine model of joint degeneration. Joints (n = 64) were grossly assessed for palmar/plantar osteochondral disease (POD) in racehorses that required euthanasia for unrelated reasons and assigned a grade of 0 (n = 34), 1 (n = 17), 2 or 3 (n = 13) using a recognized grading scheme. Synovium, cartilage, and subchondral bone were collected for histological and gene expression analysis. Relations between POD grade, cartilage histological score, and gene expression levels were examined using one-way analysis of variance or Kruskal-Wallis test and Spearman's correlation coefficient with corrections for multiple comparisons. Cartilage histological score increased in joints with POD grade 1 (p = 0.002) and 2 or 3 (p < 0.001) compared to 0. At grade 1, expression of COL1A1, COL2A1, and MMP1 increased and BGN decreased in subchondral bone while expression of BGN and ACAN decreased in cartilage. These changes further progressed at grades 2 and 3. POD grades 2 and 3 were associated with decreased expression of osteoclast inhibitor OPG and increased markers of cartilage degeneration (MMP13, COL1A1). Expression of the vascular endothelial growth factor decreased with POD grade and negatively correlated with cartilage histological score. Synovium showed no histological or transcriptomic changes related to pathology grade. Cartilage degeneration in POD is likely to be secondary to remodeling of the subchondral bone. Limited activation of proinflammatory and catabolic genes and moderate synovial pathology suggests distinct molecular phenotype of POD compared with OA.
© 2021 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals LLC.
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Publication Date: 2021-05-16 PubMed ID: 33993513DOI: 10.1002/jor.25075Google 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.

The research article investigates the correlation of pathological changes in various joint tissues using an equine model of joint degeneration. It was found that cartilage degeneration in osteochondral disease is likely secondary to the remodelling of bone beneath cartilage layers, with limited activation of pro-inflammatory and catabolic genes, implying that this disorder may have a different molecular profile than osteoarthritis.

Study Design and Methodology

  • The researchers collected and analyzed joints from 64 racehorses that had to be euthanized for unrelated reasons. These joint samples were visually examined for indications of palmar/plantar osteochondral disease (POD), an equine joint degeneration that’s naturally occurring. They were then graded on a scale of 0 to 3 using a recognized grading scheme.
  • Subchondral bone, cartilage, and synovium from each joint were collected and put through histological and gene expression analysis.
  • The relationships between the POD grades, histological scores from the cartilage, and gene expression levels were analyzed using one-way analysis of variance, or the Kruskal-Wallis test and Spearman’s correlation coefficient. Corrections were made for multiple comparisons.

Results and Findings

  • The histological score of the cartilage increased in joints with a grade 1 (p = 0.002) and 2 or 3 (p < 0.001) POD compared to those that were graded as 0. This indicates an increase in the severity of cartilage degeneration with higher POD grades.
  • The researchers observed changes in the expression of genes associated with cartilage degeneration and bone remodelling at all POD grades. There was elevated expression of COL1A1, COL2A1, and MMP1 genes and decreased expression of BGN in the subchondral bone at grade 1. These changes advanced further at higher POD grades.
  • At POD grades 2 and 3, the expression of osteoclast inhibitor OPG decreased and markers of cartilage degeneration (MMP13, COL1A1) increased.
  • The study found that the expression of the vascular endothelial growth factor (VEGF) reduced with POD grade and negatively correlated with the cartilage’s histological score. This might indicate possible connections between vascular regression and cartilage degeneration.
  • No histological or gene transcript changes related to disease severity (POD grade) were found in the synovium.

Conclusions

  • The study suggests that in POD, cartilage degeneration likely occurs due to the remodelling of the subchondral bone. Subchondral bone remodelling changes were observed to happen before major cartilage degeneration, suggesting a potential causal relationship.
  • The study observed limited activation of pro-inflammatory and catabolic genes and limited synovial pathology, suggesting a unique molecular phenotype of POD compared to more conventional cases of osteoarthritis.

Cite This Article

APA
Turlo AJ, McDermott BT, Barr ED, Riggs CM, Boyde A, Pinchbeck GL, Clegg PD. (2021). Gene expression analysis of subchondral bone, cartilage, and synovium in naturally occurring equine palmar/plantar osteochondral disease. J Orthop Res, 40(3), 595-603. https://doi.org/10.1002/jor.25075

Publication

Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
NlmUniqueID: 8404726
Country: United States
Language: English
Volume: 40
Issue: 3
Pages: 595-603

Researcher Affiliations

Turlo, Agnieszka J
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
McDermott, Benjamin T
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
Barr, Elizabeth D
  • Barr Equine Veterinary Ltd., West Malling, Kent, UK.
Riggs, Chris M
  • Department of Veterinary Clinical Services, Hong Kong Jockey Club, Sha Tin Racecourse, New Territories, Hong Kong SAR, China.
Boyde, Alan
  • Dental Physical Sciences, Oral BioEngineering, Queen Mary University of London, Mile End Campus, London, UK.
Pinchbeck, Gina L
  • Department of Epidemiology and Population Health, Institute of Infection and Global Health, School of Veterinary Science, University of Liverpool, Liverpool, UK.
Clegg, Peter D
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

MeSH Terms

  • Animals
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Cartilage / metabolism
  • Cartilage / pathology
  • Cartilage Diseases / pathology
  • Cartilage, Articular / pathology
  • Gene Expression Profiling
  • Horses
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism
  • Osteochondritis Dissecans / genetics
  • Osteochondritis Dissecans / metabolism
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • Vascular Endothelial Growth Factor A / metabolism

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Citations

This article has been cited 3 times.
  1. Lewczuk D, Wypchło M, Hecold M, Buczkowska R, Korwin-Kossakowska A. Connections Between Gene Polymorphism and Fetlock and Hock Measurements in Polish Sport Horses. Int J Mol Sci 2025 Oct 2;26(19).
    doi: 10.3390/ijms26199645pubmed: 41096909google scholar: lookup
  2. Malekipour F, Whitton RC, Lee PV. Advancements in Subchondral Bone Biomechanics: Insights from Computed Tomography and Micro-Computed Tomography Imaging in Equine Models. Curr Osteoporos Rep 2024 Dec;22(6):544-552.
    doi: 10.1007/s11914-024-00886-ypubmed: 39276168google scholar: lookup
  3. Connard SS, Gaesser AM, Clarke EJ, Linardi RL, Even KM, Engiles JB, Koch DW, Peffers MJ, Ortved KF. Plasma and synovial fluid extracellular vesicles display altered microRNA profiles in horses with naturally occurring post-traumatic osteoarthritis: an exploratory study. J Am Vet Med Assoc 2024 Jun 1;262(S1):S83-S96.
    doi: 10.2460/javma.24.02.0102pubmed: 38593834google scholar: lookup
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