Poster 2: Cell and Tissue Studies
Actin Regulates Tenocyte Gene Expression Via Mrtf
Valerie West, Kameron Inguito, Karl Matthew Ebron, Justin Parreno
University of Delaware
Tendinosis as a result of tissue overload counterintuitively causes under stimulation of tenocytes. We previously demonstrated that cellular under stimulation alters cellular phenotype through a decrease in tenogenic expression levels and an increase in both chondrogenic and protease expression levels. Therefore, we hypothesize that this regulation of genes in response to cellular stress-deprivation is the result of actin depolymerization. Specifically, that actin depolymerization regulates genes through monomeric (globular; G-) actin-binding myocardin-related transcription factor (MRTF).
We exposed isolated primary tenocytes to Latrunculin A, sequestering G-actin, preventing actin polymerization, and causing a nuclear export of MRTF from the nucleus of cells. Coinciding with nuclear export of MRTF are decreases to tenogenic genes (collagen-1, scleraxis, and a-smooth muscle actin) and increases to the expression of chondrogenic (Sox9) and proteases (Mmp-3 and Mmp-13). To determine if genes were regulated directly by MRTF, we exposed tenocytes to MRTF inhibitor, CCG1423, resulting in significant decreases to tenogenic genes with minimal effects on chondrogenic or protease genes. In conclusion, actin depolymerization is a regulator of gene expression in tendon cells, partially through regulation of MRTF. Ultimately, further understanding the regulation of gene expression during tendinosis by actin may lead to new therapeutic opportunities against disease progression.
Research Area: Ligament & Tendon