Our purpose is to gain a greater understanding of the basic cellular and molecular mechanisms that lead to tendinopathies and to translate these studies to the clinic. Tendon diseases can be painful, debilitating and significantly detract from the quality of one's life. Much of what we know about tendon fibroblast cell biology comes from in vitro cell culture studies or descriptive histological studies of diseased and healthy tissue. There has been a lack of in vivo, mechanism driven studies that combine contemporary molecular biology and genetics with precise tissue mechanics and functional measures. The long-term goal of this project is to better understand tendon fibroblast biology in the context of injury and disease, and to improve the treatment of tendinopathies. For many tissues in the body, the genes that control embryonic tissue development are also important in the repair and regeneration of adult tissues. Scleraxis is a bHLH transcription factor that is critical for the embryonic development of limb tendons, but little is known about scleraxis function in adult tendons. Our overall hypotheses are that scleraxis is important for the adaptation of tendons to mechanical loading, scleraxis is regulated by TGF-? and IGF-1 signaling pathways, and that dysregulation of scleraxis is a central factor in the development of tendinosis. These hypotheses are rigorously tested in three Specific Aims that use a multidisciplinary approach involving a combination of molecular biology and tissue mechanics experiments in adult wild type mice (ScxWT), adult transgenic mice with a postnatal inducible knockdown of scleraxis (ScxKD), and in cultured primary tendon fibroblast cells from humans and mice. These studies will provide important insight into adult tendon fibroblast physiology, and lay the groundwork for future translational studies focused on scleraxis to improve the treatment of patients suffering from tendinopathies.
to public health is based upon the tremendous impact that tendon injuries and diseases have on mobility and quality of life. There is a substantial lack in our understanding of how tendons adapt to new stresses placed upon them, and how tendons recover from injuries. Increasing our understanding of fundamental adult tendon biology and translating this to patients is highly relevant to the NIH's mission to reduce the burdens of human disability.
|Davis, Max E; Korn, Michael A; Gumucio, Jonathan P et al. (2015) Simvastatin reduces fibrosis and protects against muscle weakness after massive rotator cuff tear. J Shoulder Elbow Surg 24:280-7|
|Davis, Max E; Stafford, Patrick L; Jergenson, Matthew J et al. (2015) Muscle fibers are injured at the time of acute and chronic rotator cuff repair. Clin Orthop Relat Res 473:226-32|
|Gumucio, Jonathan P; Phan, Anthony C; Ruehlmann, David G et al. (2014) Synergist ablation induces rapid tendon growth through the synthesis of a neotendon matrix. J Appl Physiol (1985) 117:1287-91|
|Sugg, Kristoffer B; Lubardic, Jovan; Gumucio, Jonathan P et al. (2014) Changes in macrophage phenotype and induction of epithelial-to-mesenchymal transition genes following acute Achilles tenotomy and repair. J Orthop Res 32:944-51|
|Oak, Nikhil R; Gumucio, Jonathan P; Flood, Michael D et al. (2014) Inhibition of 5-LOX, COX-1, and COX-2 increases tendon healing and reduces muscle fibrosis and lipid accumulation after rotator cuff repair. Am J Sports Med 42:2860-8|