The role of microRNA 29 in tendon disease. (360G-Wellcome-100651_Z_12_Z)

Tendinopathies pose a significant, prevalent and costly musculoskeletal medicine challenge. Tendinopathy is dominated by a switch from Collagen type I to type III production resulting in biomechanically inferior tendon ultrastructure. My previous studies, invoking several model systems, directly implicate inflammatory cytokines, dysregulated apoptosis and biomechanical cellular stress in pathology. MicroRNAs (miRNAs) are short non-coding RNA that post-transcriptionally regulate gene expres sion. They are increasingly recognised to manifest central roles in a variety of human pathologies but have never been investigated in tendinopathy. MiR29 family members have however been implicated as regulators of collagen III synthesis. I recently detected significantly altered levels of miR29 family members, correlated with collagen matrix dysregulation and inflammatory infiltrate in damaged human tendon. I hypothesise that modulation of miR29 represents a novel therapeutic approach to tendon healing. I aim: 1. To define the role of miR 29 in experimental and clinical tendinopathy 2. To identify cellular pathways regulated by mir-29a in tenocytes, and by which mechanism. 3. To develop and validate targeted therapy for miR-29a using sponge technology as a miR delivery system in experimental tendon injury. Thus, I will clearly elucidate the role of miRNA 29 in tendinopathy and in so doing, define its therapeutic utility.