Roadmap of molecular, compositional, and functional markers during embryonic tendon development.

Tendon is a specialized connective tissue that connects muscle to bone, thereby enabling musculoskeletal movement. Tendon injury leads to formation of tissue with aberrant functional properties. Current approaches to treat tendon injuries, including surgical repair and tissue engineering, have not achieved normal tendon. A roadmap of markers could help with identifying when mis-steps occur during aberrant tendon formation and providing instructions for normal tendon formation. We propose this roadmap should be based on the embryo-the perfect model of tissue formation. Our prior studies have shown that adult mesenchymal stem cells mimic tendon progenitor cell behavior when treated with tendon developmental cues. Although transcription factors and extracellular matrix molecules are commonly used to assess tendon development, we have shown that these markers do not reliably reflect functional property elaboration. Thus, evaluating tendon formation on the basis of a combination of these molecular, compositional, and functional markers is important. In this review, we highlight various tendon markers with focus on their temporal profiles and roles in tendon development to outline a roadmap that may be useful for informing tendon healing and tissue engineering strategies.