Decoding the Transcriptomic Expression and Genomic Methylation Patterns in the Tendon Proper and Its Peritenon Region in the Aging Horse

OBJECTIVES:Equine tendinopathies are challenging because of the poor healing capacity of tendons commonly resulting in high re-injury rates. Within the tendon, different regions - tendon proper (TP) and peritenon (PERI) - contribute to the tendon matrix in differing capacities during injury and aging. Aged tendons have decreased repair potential; the underlying transcriptional and epigenetic changes that occur in the TP and PERI regions are not well understood. The objective of this study was to assess TP and PERI regional differences in adolescent, midlife, and geriatric horses using RNA sequencing and DNA methylation techniques.RESULTS:Differences existed between TP and PERI regions of equine superficial digital flexor tendons by age as evidenced by RNASeq and DNA methylation. Cluster analysis indicated that regional distinctions existed regardless of age. Genes such as DCN, COMP, FN1, and LOX maintained elevated TP expression while genes such as GSN and AHNAK were abundant in PERI. Increased gene activity was present in adolescent and geriatric populations but decreased during midlife. Regional differences in DNA methylation were also noted. Notably, when evaluating all ages of TP against PERI, five genes (HAND2, CHD9, RASL11B, ADGRD1, and COL14A1) had regions of differential methylation as well as differential gene expression.