Abstract: Osteoarthritis (OA) remains a major cause of lameness in horses, which leads to lost days of training and early retirement. Still, the underlying pathological processes are poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that serve as regulators of many biological processes including OA. Analysis of miRNA expression in diseased joint tissues such as cartilage and synovial membrane may help to elucidate OA pathology. Since integrin α10β1-selected mesenchymal stem cell (integrin α10-MSC) have shown mitigating effect on equine OA we here investigated the effect of integrin α10-MSCs on miRNA expression. Cartilage and synovial membrane was harvested from the middle carpal joint of horses with experimentally induced, untreated OA, horses with experimentally induced OA treated with allogeneic adipose-derived MSCs selected for the marker integrin α10-MSCs, and from healthy control joints. miRNA expression in cartilage and synovial membrane was established by quantifying 70 pre-determined miRNAs by qPCR. Differential expression of the miRNAs was evaluated by comparing untreated OA and control, untreated OA and MSC-treated OA, and joints with high and low pathology score. A total of 60 miRNAs were successfully quantified in the cartilage samples and 55 miRNAs were quantified in the synovial membrane samples. In cartilage, miR-146a, miR-150 and miR-409 had significantly higher expression in untreated OA joints than in control joints. Expression of miR-125a-3p, miR-150, miR-200c, and miR-499-5p was significantly reduced in cartilage from MSC-treated OA joints compared to the untreated OA joints. Expression of miR-139-5p, miR-150, miR-182-5p, miR-200a, miR-378, miR-409-3p, and miR-7177b in articular cartilage reflected pathology score. Several of these miRNAs are known from research in human patients with OA and from murine OA models. Our study shows that these miRNAs are also differentially expressed in experimental equine OA, and that expression depends on OA severity. Moreover, MSC treatment, which resulted in less severe OA, also affected miRNA expression in cartilage.
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The research explores the effect of mesenchymal stem cells (MSCs) selected for the marker integrin α10 on microRNA (miRNA) expression in horses with osteoarthritis. The study found that specific miRNAs show different levels of expression in joints from horses with untreated osteoarthritis versus those treated with MSCs, suggesting that MSC treatment can influence miRNA expression.
Introduction
The research is centered on osteoarthritis (OA), a significant cause of lameness in horses, contributing to lost training days and early retirement. Unfortunately, the underlying pathological processes remain poorly understood.
miRNAs are small non-coding RNAs that regulate numerous biological processes, including OA. It is believed that analyzing miRNA expression in diseased joint tissues like cartilage and synovial membrane could enlighten us about the pathology of OA.
Experimentation and Methodology
In the study, cartilage and synovial membrane were harvested from various horses: those with experimentally induced, untreated OA; those with experimentally induced OA treated with allogeneic adipose-derived MSCs selected for the marker integrin α10-MSCs, and from healthy control joints.
miRNA expression in cartilage and synovial membrane was established by quantifying 70 pre-determined miRNAs using quantitative PCR (qPCR). The differential expression of the miRNAs was evaluated by comparing various scenarios, such as untreated OA and control, untreated OA and MSC-treated OA, and joints with high and low pathology scores.
Findings and Conclusions
They found a total of 60 miRNAs quantified in the cartilage samples and 55 miRNAs in the synovial membrane samples. miRNAs like miR-146a, miR-150, and miR-409 had significantly higher expression in untreated OA joints than in control joints.
The expression of particular miRNAs was drastically reduced in cartilage from MSC-treated OA joints compared to the untreated OA joints. This suggests that MSC treatment affects miRNA expression in a way that potentially reduces OA severity.
The expression of certain miRNAs in articular cartilage also reflected the pathology score. These findings show that the miRNAs known from research in human patients with OA and from murine OA models are also differentially expressed in experimental equine OA, and their expression depends on OA severity.
Cite This Article
APA
Andersen C, Walters M, Bundgaard L, Berg LC, Vonk LA, Lundgren-Åkerlund E, Henriksen BL, Lindegaard C, Skovgaard K, Jacobsen S.
(2024).
Intraarticular treatment with integrin α10β1-selected mesenchymal stem cells affects microRNA expression in experimental post-traumatic osteoarthritis in horses.
Front Vet Sci, 11, 1374681.
https://doi.org/10.3389/fvets.2024.1374681
Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Walters, Marie
Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Bundgaard, Louise
Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Berg, Lise Charlotte
Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Vonk, Lucienne Angela
Xintela AB, Lund, Sweden.
Lundgren-Åkerlund, Evy
Xintela AB, Lund, Sweden.
Henriksen, Betina Lyngfeldt
Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
Lindegaard, Casper
Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Skovgaard, Kerstin
Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
Jacobsen, Stine
Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Conflict of Interest Statement
Authors EL-Å and LV were employed by the company Xintela AB. Author EL-Å is the CEO and CSO of Xintela AB, holds stock in the company, is an inventor of a patent related to this study. The remaining 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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