Molecular mechanisms regulating tendon regeneration and tendon cell fate

Icahn School Of Medicine At Mount Sinai, New York NY

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Abstract

Summary Achilles tendinopathy is a common degenerative change seen in athletes and elderly individuals. Tendons have limited regenerative capacity and heal via the formation of a disorganized, fibrotic scar. Surgical options for tendinopathy are often ineffective and rates of re- injury after surgical intervention are high. While the clinical changes associated with tendinopathy are well characterized, its molecular underpinnings are poorly understood. In an effort to understand the signaling pathways that control tendon healing, our lab has developed a regenerative model of tendon healing in neonatal mice to complement an already existing adult, fibrotic model. Our data suggests that regeneration is made possible, in part, by the tight coordination of ?SMA+ cells and tenocytes in concert. While tenocytes are recruited to the injury site from the tendon stubs in neonatal healing, this key component of regeneration is absent from adult fibrotic healing. Interestingly, prior literature has demonstrated that TGF? signaling is required for the activation of ?SMA+, scar-depositing myofibroblasts and for tendon development. Therefore, we hypothesize that TGF? signaling is required for ?SMA+ cell recruitment after adult healing (Aim 1) and for tenocyte recruitment in neonatal regeneration (Aim 2). Lastly, we hypothesize that the increased tenogenicity of neonatal tenocytes will rescue adult tendon healing (Aim 3).