Comparative study of in vitro osteoarthritic inflammatory models during chondrogenic differentiation in pellet culture.

Osteoarthritis (OA) treatments address pain rather than disease progression. A limitation of current in vitro testing of tissue constructs is evaluation under ideal conditions rather than inflammatory, osteoarthritic environments. To address this limitation, we evaluated mesenchymal stromal cells (MSCs) in simulated OA conditions. Our goals are to determine the effect of an OA environment on MSC pellets exposed to transforming growth factor-beta-3 (TGF-β3) and to compare OA cytokine models of tumor necrosis factor-alpha (TNF-α) and oncostatin M (OSM), TNF-α alone, or interleukin-1 beta (IL-1β) alone. Three controls were evaluated: (1) negative and (2) positive for cartilage matrix production, and (3) OSM. The IL-1β, TNF-α, and OSM + TNF-α groups all had reduced cartilage matrix production, whereas OSM showed intermediate deposition. OSM had the highest MMP-13 expression, followed by IL-1β and OSM + TNF-α. OSM + TNF-α had a sustained inflammatory response with elevated IL-6 and IL-8 gene and protein expression. Overall, MSC response to OSM + TNF-α or IL-1β alone mimicked disease phenotypes more closely than TNF-α alone. The results highlight that MSCs exposed to chondrogenic growth factors do not result in significant cartilage matrix formation in the inflammatory environment. Thus, there is a need for tissue-engineered constructs that protect cells from inflammation and promote cartilage formation.