Integrated mechanobiology of tenocytes and stem cells during tendon growth

Abstract Our purpose is to gain a greater understanding of the basic cellular and molecular mechanisms that regulate tendon growth, and to apply this knowledge to the treatment of tendinopathies and tendon injuries. Tenocytes are the major cell population in tendon. They are terminally differentiated cells which play important roles in tendon extracellular matrix (ECM) growth and remodeling. Recent work from our lab and others has identified a population of CD146+ pericytes which exist in the vasculature that directly surrounds tendon tissue. These pericytes appear able to migrate to sites of tendon growth or injury, differentiate into tenocytes, and contribute to the formation of new tendon extracellular matrix. The discovery of this new stem cell population is exciting, as it could directly lead to improved treatments for tendon disorders. Little is known about the factors that regulate the activity of these cells. Using a combination of molecular genetics, tissue mechanics, and bioinformatics techniques, our goal is to gain a greater understanding of how tenocytes respond to mechanical growth signals, and relay this information to pericytes. Our working hypothesis is that mechanical loading causes tenocytes to release factors that activate pericytes in the vasculature, which then migrate into the tendon extracellular matrix and differentiate into tenocytes. These studies will provide important insight into adult tenocyte and tendon stem cell biology, and lay the groundwork for future translational studies to improve the treatment of tendinopathies and tendon injuries.