Next-generation sequencing identifies equine cartilage and subchondral bone miRNAs and suggests their involvement in osteochondrosis physiopathology.
Abstract: MicroRNAs (miRNAs) are an abundant class of small single-stranded non-coding RNA molecules ranging from 18 to 24 nucleotides. They negatively regulate gene expression at the post-transcriptional level and play key roles in many biological processes, including skeletal development and cartilage maturation. In addition, miRNAs involvement in osteoarticular diseases has been proved and some of them were identified as suitable biomarkers for pathological conditions. Equine osteochondrosis (OC) is one of the most prevalent juvenile osteoarticular disorders in horses and represents a major concern for animal welfare and economic reasons. Its etiology and pathology remain controversial and biological pathways as well as molecular mechanisms involved in the physiopathology are still unclear. This study aims to investigate the potential role of miRNAs in equine osteochondrosis (OC) physiopathology.Short-read NGS technology (SOLID™, Life Technologies) was used to establish a comprehensive repertoire of miRNA expressed in either equine cartilage or subchondral bone. Undamaged cartilage and subchondral bone samples from healthy (healthy samples) and OC-affected (predisposed samples) 10-month Anglo-Arabian foals were analysed. Samples were also subjected or not to an experimental mechanical loading to evaluate the role of miRNAs in the regulation of mechano-transduction pathways. Predicted targets of annotated miRNAs were identified using miRmap. Results: Epiphyseal cartilage and subchondral bone miRNome were defined, including about 300 new miRNAs. Differentially expressed miRNAs were identified between bone and cartilage from healthy and OC foals, as well as after an experimental mechanical loading. In cartilage, functional annotation of their predicted targets suggests a role in the maintenance of cartilage integrity through the control of cell cycle and differentiation, energy production and metabolism as well as extracellular matrix structure and dynamics. In bone, miRNA predicited targets were associated with osteoblasts and osteoclasts differentiation, though the regulation of energy production, vesicle transport and some growth factor signaling pathways. Conclusions: Taken together, our results suggest a role of miRNAs in equine OC physiopathology and in the cellular response to biomechanical stress in cartilage and bone. In silico target prediction and functional enrichment analysis provides new insight into OC molecular physiopathology.
Publication Date: 2014-09-17 PubMed ID: 25227120PubMed Central: PMC4190437DOI: 10.1186/1471-2164-15-798Google Scholar: Lookup
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- Journal Article
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- Non-U.S. Gov't
Summary
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This study investigates the role of miRNAs, or small non-coding RNA molecules, in the development and pathology of equine osteochondrosis, a common juvenile skeletal disorder in horses. By utilizing short-read next-generation sequencing, the researchers identified miRNAs related to cartilage and bone health and examined their influence on this disease.
Overview of the Research
- This research focused on uncovering the role of microRNAs (miRNAs) in equine osteochondrosis (OC), a prevalent osteoarticular disease in horses. MiRNAs are small, single-stranded non-coding RNA molecules that regulate gene expression at the post-transcriptional level, playing vital roles in several biological processes, including skeletal development and cartilage maturation. They’ve also shown involvement in osteoarticular diseases, making them potential biomarkers for such conditions.
- The pathology and etiology of equine OC are not entirely understood, which prompted the researchers to look into potential molecular mechanisms, including the role of miRNAs.
Methodology of the Study
- The researchers made use of Short-read NGS technology from SOLiD™, Life Technologies, to gather a comprehensive list of miRNAs found in equine cartilage or subchondral bone.
- They collected and examined both damaged and healthy cartilage and subchondral bone samples from 10-month old Anglo-Arabian foals. Some samples were subjected to experimental mechanical loading to explore miRNAs role in mechano-transduction pathways regulation.
- The researchers used a program called miRmap to identify predicted targets of the annotated miRNAs.
Results and Conclusions
- The research resulted in defining the epiphyseal cartilage and subchondral bone miRNome, which included approximately 300 new miRNAs. Some miRNAs expressed differently between bone and cartilage in healthy foals and those with OC, and after experimental mechanical loading.
- Analysis of the predicted targets in cartilage suggests a role of miRNAs in maintaining cartilage integrity through regulation of cell cycle, differentiation, energy production, metabolism, and structure/dynamics of the extracellular matrix. Meanwhile, in bone, miRNA targets were associated with osteoblasts and osteoclasts differentiation through energy production, vesicle transport, and growth factor signaling pathways regulation.
- The collective results suggested a potential role of miRNAs in the physiopathology of equine OC and how cells respond to biomechanical stress in cartilage and bone. They offer new perspectives on the molecular physiopathology of OC, paving the way for further research and potentially the development of new diagnostics or therapies.
Cite This Article
APA
Desjardin C, Vaiman A, Mata X, Legendre R, Laubier J, Kennedy SP, Laloe D, Barrey E, Jacques C, Cribiu EP, Schibler L.
(2014).
Next-generation sequencing identifies equine cartilage and subchondral bone miRNAs and suggests their involvement in osteochondrosis physiopathology.
BMC Genomics, 15(1), 798.
https://doi.org/10.1186/1471-2164-15-798 Publication
Researcher Affiliations
- INRA, UMR1313 Génétique animale et biologie intégrative, Domaine de Vilvert, 78350 Jouy-en-Josas, France. clemence.desjardin@jouy.inra.fr.
MeSH Terms
- Animals
- Biomechanical Phenomena
- Bone and Bones / metabolism
- Bone and Bones / physiopathology
- Cartilage / metabolism
- Cartilage / physiopathology
- High-Throughput Nucleotide Sequencing
- Horse Diseases / genetics
- Horse Diseases / physiopathology
- Horses / genetics
- MicroRNAs / genetics
- Molecular Sequence Annotation
- Osteochondrosis / genetics
- Osteochondrosis / physiopathology
- Sequence Analysis, RNA
- Weight-Bearing
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