Abstract: Synovial macrophages' role in equine osteoarthritis (OA) is not well understood, despite horses being a model for human degenerative joint disorders. Equine synovial macrophages' characterization is limited and age-related changes are not described. This study aimed to evaluate surface marker distribution and expression from potential synovial tissue macrophages in foals, adult non-affected, and OA-affected horses. Unassigned: Surface markers (CD14, CD16, CD206) were quantitatively evaluated on dorsal villous synovial biopsies from the metacarpophalangeal joint of foals (F), non-affected (control; CTRL), and OA-affected adults (OA) using immunofluorescence histology and computed image analysis. Samples were analyzed in three regions: intimal cell layer (ICL), subintimal tissue layer of the villous region (SI-V), and subintimal tissue layer not associated with the villous region (SI-N). Synovial fluid protein, cytokine, and chemokine concentrations, and hematoxylin-eosin (HE) staining were performed to assess joint disease state. Unassigned: Marker-associated areas were increased in ICL and SI-V compared to SI-N for all three groups. The CD14 area was increased in the CTRL when compared to the OA and F groups (ICL, SI-V). CD16 areas were similar in all groups, while CD206+ area was larger in foals compared to CTRL and OA groups (ICL, SI-V). Synovial fluid cytokine and chemokine concentrations did not differ between groups. Unassigned: Computed analysis of immunofluorescence staining of CD14, CD16, and CD206 on equine synovial tissue revealed region specific marker expressions. While an altered marker expression in relation to age and degenerative joint disease was shown, further investigation is required to determine marker significance for identifying equine synovial tissue macrophages.
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Overview
This research investigates the presence and distribution of specific immune cell markers on synovial tissue macrophages in horse joints, focusing on differences related to age and osteoarthritis (OA) status.
The study aims to better understand how macrophages in equine synovial tissue vary between young foals, healthy adults, and adults with OA, providing insight that might be relevant to human joint diseases.
Background and Purpose
Osteoarthritis is a degenerative joint disease affecting both humans and horses, characterized by joint tissue degradation.
Synovial macrophages are immune cells resident in the joint lining that may play a role in OA progression, but their specific functions and marker profiles in horses are poorly understood.
The equine metacarpophalangeal joint (a joint in the horse’s leg similar to the human knuckle) serves as a useful model for studying joint diseases.
The study aimed to characterize macrophage surface markers—CD14, CD16, and CD206—in synovial tissue from different age groups (foals versus adult horses) and OA status (healthy versus OA-affected).
Methods
Sample Collection:
Synovial tissue biopsies were collected from the dorsal villous region of the metacarpophalangeal joint in three groups: foals (young horses), healthy adult controls, and adult horses with osteoarthritis.
Immunofluorescence Histology:
Using antibodies against the markers CD14, CD16, and CD206, tissue sections were stained to visualize the presence and distribution of these markers.
Image Analysis:
Computed quantitative image analysis was used to measure the marker-positive areas within different regions of the synovial tissue:
Intimal cell layer (ICL) – the innermost lining of the synovium
Subintimal villous region (SI-V) – deeper tissue under the villous projections
Subintimal non-villous region (SI-N) – subintimal tissue not associated with villi
Additional Assessments:
Synovial fluid was analyzed for protein, cytokine, and chemokine levels to evaluate joint inflammation and disease state.
Hematoxylin-eosin (HE) staining was performed for histopathological evaluation of tissue structure and disease severity.
Key Findings
Marker Distribution:
CD14, CD16, and CD206 markers showed distinct region-specific expression, with higher marker-positive areas in the ICL and SI-V regions than in the SI-N region across all groups.
Age and Disease Related Differences:
CD14 expression was significantly higher in healthy adults (CTRL) than in both foals and OA-affected adults, notably in the ICL and SI-V.
CD16 expression levels were similar among all groups, showing no significant variation with age or OA status.
CD206 expression was greater in foals compared to both healthy and OA-affected adults in the ICL and SI-V regions, suggesting potential developmental changes.
Synovial Fluid Analysis:
The concentrations of cytokines and chemokines in synovial fluid did not differ significantly among the groups, indicating that systemic inflammatory markers were similar despite tissue differences.
Interpretations and Conclusions
Region-Specific Expression:
The enriched expression of macrophage markers in the innermost synovial layers (ICL and SI-V) suggests these areas are primary sites of macrophage activity in joints.
Age and Disease Influence:
Differences in marker expression between foals and adults indicate that synovial macrophage populations or phenotypes change with age.
The reduced CD14 in OA joints may reflect alterations in macrophage subtypes or functions related to disease processes.
The high CD206 in foals might suggest a more anti-inflammatory or developmental macrophage phenotype in young joints.
Challenges and Future Directions:
The precise role and significance of these markers in identifying functionally distinct macrophage populations remain unclear.
Since synovial fluid inflammatory markers did not differ, additional studies should examine local tissue-level macrophage functions in OA progression.
Further research will help clarify how macrophage populations contribute to joint health and osteoarthritis, potentially aiding therapeutic development.
Cite This Article
APA
Liso G, Winter K, Triebe TJ, Ulrich R, Brehm W, Wagner B, Schnabel CL, Troillet A, Roth SP.
(2026).
Immunohistological characterization of equine synovial tissue in metacarpophalangeal joints of different ages and osteoarthritis status.
Osteoarthr Cartil Open, 8(3), 100819.
https://doi.org/10.1016/j.ocarto.2026.100819
Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, Leipzig, Germany.
Veterinary Teaching Hospital, Department for Horses, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Winter, Karsten
Institute of Anatomy, Leipzig University, Leipzig, Germany.
Triebe, Theresa Jenny
Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, Leipzig, Germany.
Veterinary Teaching Hospital, Department for Horses, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Ulrich, Reiner
Institute of Veterinary Pathology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Brehm, Walter
Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, Leipzig, Germany.
Veterinary Teaching Hospital, Department for Horses, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Wagner, Bettina
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States of America.
Schnabel, Christiane Liliane
Institute of Immunology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Troillet, Antonia
Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, Leipzig, Germany.
Veterinary Teaching Hospital, Department for Horses, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Roth, Susanne Pauline
Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, Leipzig, Germany.
Veterinary Teaching Hospital, Department for Horses, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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