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.
Highlights
IntroductionSkeletogenesis is a complex process that is tightly regulated via the interactions of various transcription factors, growth factors and cytokines on progenitor cells of mesenchymal (osteoblast, chondrocyte) and hematopoietic (osteoclast) origin [1,2,3]
Skeletogenesis is a complex process that is tightly regulated via the interactions of various transcription factors, growth factors and cytokines on progenitor cells of mesenchymal and hematopoietic origin [1,2,3]
1115 and 3574 genes were differentially expressed between age groups in articular cartilage (AC) and subchondral bone (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
Summary
Skeletogenesis is a complex process that is tightly regulated via the interactions of various transcription factors, growth factors and cytokines on progenitor cells of mesenchymal (osteoblast, chondrocyte) and hematopoietic (osteoclast) origin [1,2,3]. Long bones are formed via endochondral ossification, the process whereby the cartilage anlage ossifies and becomes bone. Most skeletal development occurs in the fetus during gestation, endochondral ossification continues in the post-natal period at the growth plate and articular-ephiphyseal cartilage complex until the time of skeletal maturity [3]. Our understanding of the genes and pathways involved in normal skeletogenesis has been largely driven by studies of morphogenesis in model species, including mice [6,7], zebrafish [8], chickens [9], and amphibians [10,11], and by investigation of severe skeletal dysplasias in humans [1].
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