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This study investigates the transcriptome response of meniscus fibrochondrocytes (MFCs) to the low oxygen and mechanical loading signals experienced in the knee joint using a model system. We hypothesized that short term exposure to the combined treatment would promote a matrix-forming phenotype supportive of inner meniscus tissue formation. Human MFCs on a collagen scaffold were stimulated to form fibrocartilage over 6 weeks under normoxic (NRX, 20% O 2 ) conditions with supplemented TGF-β3. Tissues experienced a delayed 24h hypoxia treatment (HYP, 3% O 2 ) and then 5 min of dynamic compression (DC) between 30 and 40% strain. Delayed HYP induced an anabolic and anti-catabolic expression profile for hyaline cartilage matrix markers, while DC induced an inflammatory matrix remodeling response along with upregulation of both SOX9 and COL1A1 . There were 41 genes regulated by both HYP and DC. Overall, the combined treatment supported a unique gene expression profile favouring the hyaline cartilage aspect of inner meniscus matrix and matrix remodeling.