Injury Response in Normal Tendons: Regulatory Roles of Collagen V

Students

2018
College

Faculty

Fairhill Professor of Orthopaedic Surgery and Professor of Bioengineering

Project Summary

Collagen V, although a quantitatively minor component (2%) of mature tendons and ligaments, is a major regulator of fibrillogenesis, the formation of new collagen fibers. Collagen V plays a critical role during the early process of fibril nucleation, and reduction of collagen V expression during development results in fewer collagen I fibrils with increased diameters in tendons, ligaments, dermis, and cornea. Given the importance of the collagen I structure to tendon function, changes in the structure and/or composition of the matrix via regulation with collagen V may have dramatic effects on tendon/ligament mechanical properties. Thus, the overall goal of this project was to define the regulatory roles of collagen V in the injury response in normal (WT prior to inducing knockout) tendons using inducible collagen V-null and heterozygous models that allowed for temporal targeting of collagen V deficiency.

The mechanistic roles of collagen V in the tendon injury response were probed through histological analysis 1 week, 3 weeks, and 6 weeks after injury. Decreased collagen V expression (via genetic inactivation) at the time of injury (TM0) resulted in no significant impairment of wound matrix deposition and integration into the surrounding matrix, as indicated by computational quantification of cellularity, or cell density, and cell shape, or roundness, across time points. Ongoing work will increase sample size of these analyses. Additionally, mechanical testing will assess the structural integrity of such temporally targeted tendons. Our primary objective is to compare the roles of collagen V knockout during the late inflammatory phase (5-7 days post-injury) and the remodeling phase (21 days post-injury).  

Participating in research has greatly enriched my educational experience. As a pre-medical student, I have come to appreciate the impact of research on clinical outcomes; I found that basic scientific discovery and clinical practice interact intimately to inform clinical medicine. From a perspective of personal growth, participation in research has taught me to cope and manage failures that are inherent in the pursuit of novel scientific discovery. Lastly, looking forward, the exhilaration of identifying the fundamental relationships and mechanisms of tendon and ligament injury, healing, repair, and regeneration in order to develop new treatment modalities has left me with the continued desire to participate in and contribute to musculoskeletal research in the future.