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).

Public Health Relevance

The parent grant investigates the hypothesis that TGF? signaling mediates tenocyte recruitment after neonatal healing and ?SMA+ cell recruitment after adult healing by using TGF?RII conditional knockout mice in each cell type and injury model. We also plan to test the ability of neonatal tenocytes to rescue adult tendon healing. This fellowship will aid our ability to treat tendinopathies by identifying the molecular and cellular mechanisms which underpin tenogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AR073626-02
Application #
9972740
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kirilusha, Anthony G
Project Start
2019-08-01
Project End
2021-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Orthopedics
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029