Genome-wide alterations in DNA methylation identify Leprel2, Foxf1, Mmp25, Igfbp6 and Peg12 as disease-associated genes in murine Achilles tendinopathy

We partnered with Zymo Research, Inc. to detect genome-wide methylation changes associated with the initiation and progression of tendinopathy induced by TGF-β1 in a murine Achilles tendon model. All genes identified as significantly differentially methylated were present in only one experimental group showing that both the gene identified and its modified methylation status are dependent on the injury time-course and activity level. In summary, we identified five genes (Leprel2, Foxf1, Mmp25, Igfbp6 and Peg12) which demonstrate significant relevance to tendon biology with three exhibiting functions in collagen fibril organization. We postulate that a study of the molecular genomics of these genes in animal and human tendon could further delineate the pathogenesis of this multifactorial disease. Chronic Achilles tendinopathy was induced in WT C57/Bl6 male mice via two injections of TGF-β1 directly into the body of the tendon. Methylome analysis was conducted on the tendon DNA for the acute (3 day) response as well as the chronic response (14 and 28 days) under normal cage activity or with treadmill running and compared to un-injured mice.