Age related ephrin changes and importance of ephrin-integrin crosstalk in tendon

• Applicant: Dr. Tzvetan Popov
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 218731501

Tendon is a fibrous connective tissue that connects muscle to bone and is composed of collagen Irich extracellular matrix produced by specialized cells called tenocytes. Clinically, tendon regeneration and healing represent an enormous medical challenge because of tendon poor response to treatments resulting in prolonged rehabilitation periods. Tenocytes form a complex three-dimensional network via cell processes that mediates communication between neighboring cells and synchronizes the tissue response to mechanical loads. Among the membrane-associated proteins which could participate in such interactions, ephrins may play a central role. Ligand-induced ephrin receptor activation generates bidirectional signals and is responsible for controlling a number of cellular functions such as adhesion, proliferation, and migration. Nonetheless, the ephrin effects on these processes are often the consequence of modulation of the integrin receptor activity. In this proposal, I aim first to investigate the basal expression of ephrins in young tenocytes, second to analyze the ephrin changes in tendon aging and third to examine the possible molecular pathways involved in the ephrins-mediated control over integrin activation. Finally, I will evaluate ephrin expression and activity in integrin-deficient human and mouse tenocytes in order to decipher the importance of integrin signaling in the ephrin-integrin crosstalk.I believe this project will highlight the necessity of both ephrin and integrin signaling for normal tenocyte behavior. Knowing more about ephrin functions in tenocytes will likely contribute to a better understanding of the complex mechanism behind tendon aging. Furthermore, the gathered knowledge from this study may help science and medicine to develop novel strategies to improve the treatment of aged tendons or even to prevent or reverse tendon aging.

• DFG Programme: Research Grants