Researcher(s)
- Mark Arranguez, Human Physiology, University of Delaware
Faculty Mentor(s)
- Justin Parreno, Biological Sciences, University of Delaware
Abstract
Following injury, the inability of articular cartilage to self-repair leads to osteoarthritis (OA) progression. OA is marked by a shift in cartilage homeostasis toward matrix degradation, leading to articular cartilage breakdown. In a surgical OA model, studies have shown one of the most affected pathways to be the actin cytoskeleton, a structure essential for maintaining chondrocyte shape and function. Prior research has shown that filamentous (F-)actin reorganization can strongly influence chondrocyte behavior; therefore, maintaining proper F-actin organization may be critical for cartilage health. In this study, we elucidate the regulation of F-actin stability by F-actin stabilization proteins, the Tropomyosins (Tpms). We hypothesize that the Tpm3.1 isoform is a key regulator of F-actin polymerization. Using confocal microscopy, we examined the localization of TPM3.1 in chondrocytes, both in native mouse hip tissue sections and in vitro in isolated primary bovine cells. We determined that both TPM3.1 inhibition and Tpm3.1 knockout (KO) decreases F-actin. Additionally, while TPM3.1 inhibition led to negatively altered chondrocyte homeostasis, we did not see similar results for Tpm3.1 KO. However, using an ex vivo culturing methodology developed by our laboratory to simulate OA-like conditions, we found an exacerbated loss of F-actin in the hips of Tpm3.1 KO mice. Currently, we are investigating if the culture of femoral heads from Tpm3.1 KO mice will enhance chondrocyte matrix catabolism. Therefore, this data supports the idea that F-actin polymerization is regulated by Tpm3.1 in both mouse and bovine models. Our ex vivo model will provide further insight into the regulation of OA pathogenesis via the actin cytoskeleton.