POS0407 CHEMICALLY AND MECHANICALLY ACTIVATED PIEZO1 LEADS TO CHANGES IN THE EXPRESSION OF ECM-MODULATING FACTORS THAT DIFFER BETWEEN HEALTHY AND HUMAN OA CHONDROCYTES

Background Osteoarthritis (OA) is the most common degenerative joint disease that causes functional limitations in addition to pain and has become a major global health problem recent decades. Meta-analysis of studies on patients with knee OA showed physical exercise can function as clinically relevant, effective intervention non-drug treatment for reducing improving activity [1]. In chondrocytes, perception transduction mechanical signals leading changes [Ca 2+] i orchestrated by mechanosensitive ion channels [2]. Objectives Piezo1 represents cation channel (MSC) allows Ca 2+ influx chondrocytes acts an important mechanotransducer senses deleterious stresses (high strains) [3]. Numerous have shown regulation conjunction stimulation crucial behaviour balanced assembly ECM. The underlying mechanism could influence expression profile consequence stimulation. Differences this regard between primary human isolated from knees (pCHOA) healthy explain altered sensitivity stimuli OA. Methods Mechanical was performed use flexcell system whereas parallel cells were chemically activated via different concentrations Piezo agonist Yoda1. Changes analysed qPCR metalloproteinases (MMP1, 3,13), inflammatory cytokines (IL6, IL8, IL4) ECM relevant components (Col-I, Col-II, BMP2). decreased Yoda1 siRNA knockdown used more clearly map effect MSC under Results Chondrocytes responded tension MMP3 IL6, application resulted opposite effect. MMP enhanced than both cell types same reduction TIMP-2 through activation detected. increased IL6 IL8 while IL4 reduced. knock-out partially reverse these effects. Conclusion Performing context targeting may reveal OA-specific mechanisms signal transduction. Furthermore, provide further insight into extent which exhibit differential sensitization signals. References [1]Sasaka, R., Honda, Y., Oga, S., et al. Effect and/or educational interventions hip/knee osteoarthritis: A systematic review meta-analysis. Plos One . 2022, 21;17(11),e0275591. [2]Zhang, K., Lifu, W., Liu Z., Mechanosensory mechanotransductive processes mediated articular chondrocytes: Potential therapeutic targets osteoarthritis. Channels (Austin ). 2021 , 15(1):339-359. [3]Du, G., Li, L., Zhang, X., Roles TRPV4 Stretch-Evoked Ca2+ Response Chondrocytes. Exp. Biol. Med 2020 245(3), 180–189. Acknowledgements: NIL. Disclosure Interests None Declared.