POS0225 FLUIDIC SHEAR STRESS REDUCES TNFΑ-MEDIATED CARTILAGE DAMAGE IN A 3D MODEL OF DEGENERATIVE JOINT DISEASE

Background Pathomechanisms of degenerative joint diseases such as osteoarthritis (OA) ultimately result in the breakdown cartilage tissue. To date, exact underlying mechanisms both cause and progression OA remain unclear. Therefore, developing complex long-lasting vitro components a human including cartilage, subchondral bone, synovial membrane tendons that simulate 3D architecture metabolic, humoral cellular interplay is needed to study course pathogenesis. Beside impact metabolic architecture, mechanical forces are well-known be important modulators health, while aberrant primary etiological factors leading degeneration. Objectives Here, we aimed (i) develop model using alternated perfused cultivation (ii) TNFα-mediated degradation. As force used perfusion-mediated fluid shear stress (FSS) enhance chondrogenesis mimic FSS during movement. Methods Human bone marrow-derived mesenchymal stromal cells (MSC) were an incubated bioreactor with perfusion cycle facilitates stimulation via daily sampling. Within bioreactor, MSC mass cultures subjected at 10 dyn/cm 2 by medium circulation three times day for 1.5 hours. The approach optimized rate, cycles period 18 days was compared non-perfused control based on cell viability (live-dead- viability-assay), apoptosis (TUNEL-assay, caspase-3/7-activity, BCL2/BAX ), activity (oxygen glucose consumption, lactate production), chondrogenic gene expression ( ACAN, COMP , COL2A1, COL1A1 COL2A1/COL1A1 ) matrix metalloproteinase (MMP-1, -3, -13 ). Results Alternate long-term did not affect survival; it rather reduced apoptosis, oxygen consumption but production enhanced MMP13 conditions. Mimicking pathophysiology stimulated 100 ng/mL TNFα 6 hours under stimulus. Compared untreated conditions, overall survival (demonstrating efficacy stimulation), glycolysis, (iii) MMP1 markers protein turnover. In comparison treated TNF conditions measure IL6 soluble amounts IL-6 TNFA whereas enhanced. Furthermore, (iv) degrading enzymes (v) anabolic proteins mRNA. Conclusion mimics OA, stimulus provides “feel-good” niche reduces chondrocyte activity, expression, increases protects against Acknowledgements This project funded Sanofi-Aventis Deutschland GmbH. Disclosure Interests Duc Ha Do Nguyen: None declared, Christina Lubahn: Thomas Leeuw Employee of: Sanofi employee may hold shares and/or stock options company., Frank Buttgereit: Timo Gaber: Alexandra Damerau: declared