Podium 2: Osteoarthritis, Treatments & Mechanisms
The Regulation Of Proteoglycan 4 Via F-Actin Reorganization In Native Superficial Zone Chondrocytes
Sofia Gonzalez-Nolde, Zsanaia Badiang, Cameron Schweiger, Justin Parreno
University of Delaware
The initial stage of Osteoarthritis (OA) includes a decrease in surface lubricant proteoglycan 4 (Prg4), secreted by superficial zone chondrocytes (SZCs). Prg4 has been shown to be regulated via the actin cytoskeleton in vitro however, it remains unclear if F-actin reorganizes and regulates Prg4 in native cartilage. We develop imaging methodology of an ex vivo whole organ culture of mouse femoral head cartilage to test the hypothesis that Prg4 is regulated by F-actin in native SZCs. Culturing native cartilage in serum free DMEM results in decreased Prg4 mRNA levels. We assessed actin reorganization by the F/G-actin ratio in SZCs captured via en face images of F- and globular (G-) actin. We determined that the reduction of Prg4 via culturing correlated with a decrease in the F/G-actin ratio. Treatment with transforming growth factor beta (TGF-?) sustains the SZC F/G-actin ratio and increases Prg4 expression. We found Tropomyosin3.1 (Tpm3.1), an F-actin stabilizer, regulates Prg4; with Tpm3.1 inhibition and in Tpm3.1 KO cartilage, induction of Prg4 via TGF-? is repressed. Our findings support that Prg4 is regulated by F-actin reorganization and that Tpm3.1 is critical for growth factor induced Prg4 expression.
Research Area: Cartilage