- Mark Arranguez, Human Physiology, University of Delaware
- Justin Parreno, Biological Sciences, University of Delaware
Arthritis is a debilitating disease and is a common cause of disability in adults as >700,000 people undergo joint replacement surgery predominantly for osteoarthritis (OA) each year in the US. In the process of osteoarthritis, cartilage cells (chondrocytes) become activated and cause degeneration. We recently discovered that in early OA, the F-actin cytoskeleton within chondrocytes is reduced, contributing to chondrocyte activation. Therefore, we speculate that maintaining F-actin structure in chondrocytes is vital to preventing OA. Tropomyosins (Tpms) are a family of over 40 isoforms of F-actin binding proteins. Each isoform has a unique capability to bind to, and stabilize, F-actin. We determined that chondrocytes express two isoforms of Tpm, Tpm3.1 and Tpm4.2. In this study, we test the hypothesis that Tpm3.1 regulates chondrocyte F-actin organization and phenotype. Using Tpm3.1 Knockout (KO) mice, we examined the role of Tpm3.1 on gross hip cartilage morphology, cellular organization, chondrocyte F-actin, and Proteoglycan-4 (PRG4) mRNA levels. At the gross level, Tpm3.1 KO hip cartilage appears healthy; the hip cartilage appears smooth and thick similar to Wild Type (WT). Chondrocytes have a similar zonal organization between KO and WT. Phalloidin staining for F-actin reveals both KO and WT superficial zone chondrocytes (SZCs) are discoidal in shape and deeper zone chondrocytes are round. Furthermore, SZCs’ cortical F-actin had reduced fluorescence intensities in Tpm3.1 KO compared to WT. RT-PCR also reveals that Tpm3.1 KO leads to reduced induction of PRG4. In conclusion, this study shows that Tpm3.1 KO affects SZC phenotype. Loss of superficial zone function may lead to accelerated OA. Thus, ongoing studies aim to determine if Tpm3.1 knockout may contribute to decreased F-actin stabilization, bolstering cartilage degeneration in a post-traumatic OA model.