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.

Identification of a global gene expression signature associated with the genetic risk of catastrophic fracture in iPSC-derived osteoblasts from Thoroughbred horses

“…Of these, 27 are unannotated, 43 have published roles in bone formation or fracture and 42 have no known role in bone formation of fracture. However, of these 42 genes, all but five of them have been reported to be expressed in equine bone tissue in publicly available datasets (Kuemmerle et al, 2016, Kemper et al, 2019.…”

“…Of these, 27 are unannotated, 43 have published roles in bone formation or fracture and 42 have no known role in bone formation of fracture. However, of these 42 genes, all but five of them have been reported to be expressed in equine bone tissue in publicly available datasets (Kuemmerle et al, 2016, Kemper et al, 2019). Furthermore, STRING analyses demonstrated that 18 of the 42 genes with no known role in bone encode proteins which interact (directly or indirectly) with proteins that have known roles in bone.…”

“…However, the expression of both genes has been detected in horse bone tissue, and/or or cultured horse cells (Kuemmerle et al, 2016). CABP1 is also in the top 10 and although it has no published role in bone, it appears in the main interaction node of the STRING analysis, is a calcium binding protein and is expressed in horse bone tissue (Kuemmerle et al, 2016, Kemper et al, 2019).…”

Cardiac ion channel expression in the equine model ‐ In‐silico prediction utilising RNA sequencing data from mixed tissue samples

“…In addition, some tissues can have very heterogenous cellular composition and therefore gene expression pattern. For example, different brain region (Khaitovich et al, 2004) or different muscle fibres types (Rubenstein et al, 2020) can display different gene expression profile. This is especially the case in the heart where previous studies in other species have demonstrated differing ion channel expression not only between atria and ventricles but also within different regions of each chamber such as between the epicardium and myocardium (Bartos et al, 2015;Saadeh, Chadda, et al, 2020;Schram et al, 2002;).…”

Vitamin K and equine osteocalcin: an enigma explored

“…This can lead to subchondral fractures, cysts, cartilage flaps and synovitis (Olstad et al 2011). Much research has studied possible causative factors including genetics, and diet, the relative contribution of which appears to vary (Coskun et al 2016;Kemper et al 2019). Osteoporosis and osteoarthritis in humans, resemble OCDs in horses with loss of articular cartilage and degeneration.…”