Differential Gene Expression in Articular Cartilage and Subchondral Bone of Neonatal and Adult Horses.
Abstract: Skeletogenesis is complex and incompletely understood. Derangement of this process likely underlies developmental skeletal pathologies. Examination of tissue-specific gene expression may help elucidate novel skeletal developmental pathways that could contribute to disease risk. Our aim was to identify and functionally annotate differentially expressed genes in equine neonatal and adult articular cartilage (AC) and subchondral bone (SCB). RNA was sequenced from healthy AC and SCB from the fetlock, hock, and stifle joints of 6 foals (≤4 weeks of age) and six adults (8-12 years of age). There was distinct clustering by age and tissue type. After differential expression analysis, functional annotation and pathway analysis were performed using PANTHER and Reactome. Approximately 1115 and 3574 genes were differentially expressed between age groups in AC and SCB, respectively, falling within dozens of overrepresented gene ontology terms and enriched pathways reflecting a state of growth, high metabolic activity, and tissue turnover in the foals. Enriched pathways were dominated by those related to extracellular matrix organization and turnover, and cell cycle and signal transduction. Additionally, we identified enriched pathways related to neural development and neurotransmission in AC and innate immunity in SCB. These represent novel potential mechanisms for disease that can be explored in future work.
Publication Date: 2019-09-25 PubMed ID: 31557843PubMed Central: PMC6826356DOI: 10.3390/genes10100745Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This research aimed to investigate the differences in gene expression in the cartilage and bone of newborn and adult horses, and how these differences could potentially be related to developmental skeletal diseases.
Research Methodology
- The researchers extracted RNA from healthy articular cartilage (AC) and subchondral bone (SCB) harvested from the fetlock, hock, and stifle joints of six foals (newborn horses ≤4 weeks of age) and six adult horses (8-12 years of age).
- This extracted RNA was sequenced to identify the range of genes expressed in each sample.
- The team used differential expression analysis to identify genes that were expressed at different amounts in the neonatal versus adult samples. This led to the discovery of approximately 1115 differentially expressed genes in the AC and 3574 in the SCB of foals compared to adults.
- These differentially expressed genes were then categorized according to their associated biological functions, known as gene ontology terms, and assigned to specific biological pathways through functional annotation and pathway analysis using PANTHER and Reactome, two dedicated bioinformatics tools.
Major Findings
- The study found that there was distinct clustering by age and tissue type, with the foals exhibiting a state of growth, high metabolic activity, and tissue turnover.
- The researchers also identified several overrepresented gene ontology terms and enriched pathways, dominated by those related to extracellular matrix organization and turnover, cell cycle, and signal transduction.
- Additionally, they discovered pathways related to neural development and neurotransmission in the AC, and innate immunity in the SCB, providing novel directions for future research into the potential mechanisms underlying disease.
Implications and Next Steps
- The results of this study provide important insights into the differential gene expression occurring in neonatal versus adult horse cartilage and bone. This knowledge could help inform our understanding of skeletal development, and may even contribute to identifying potential new biomarkers for disease risk.
- The researchers have identified several novel pathways which could potentially play a role in the development of disease. These findings pave the way for future investigations to further validate these pathways and to determine their precise role in disease development and progression.
Cite This Article
APA
Kemper AM, Drnevich J, McCue ME, McCoy AM.
(2019).
Differential Gene Expression in Articular Cartilage and Subchondral Bone of Neonatal and Adult Horses.
Genes (Basel), 10(10), 745.
https://doi.org/10.3390/genes10100745 Publication
Researcher Affiliations
- Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, IL 61802, USA. amkemper@illinois.edu.
- Roy J. Carver Biotechnology Center, University of Illinois, Urbana, IL 61801, USA. drnevich@illinois.edu.
- Veterinary Population Medicine Department, University of Minnesota College of Veterinary Medicine, St. Paul, MN 55108, USA. mccų@umn.edu.
- Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, IL 61802, USA. mccoya@illinois.edu.
MeSH Terms
- Animals
- Animals, Newborn / genetics
- Bone and Bones / metabolism
- Cartilage, Articular / metabolism
- Female
- Gene Expression
- Horses / genetics
- Male
- Sequence Analysis, RNA
- Transcriptome
Conflict of Interest Statement
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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Citations
This article has been cited 1 times.- Premont A, Saadeh K, Edling C, Lewis R, Marr CM, Jeevaratnam K. Cardiac ion channel expression in the equine model - In-silico prediction utilising RNA sequencing data from mixed tissue samples.. Physiol Rep 2022 Jul;10(14):e15273.
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