Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression

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 6weeks under normoxic (NRX, 20% O2) conditions with supplemented TGF -ß3. Tissues experienced a delayed 24h hypoxia treatment (HYP, 3% O2) and then 5min 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. Overall design: Examination completed using 18 sequenced samples. These came from 3 mensicus donors (6 samples per donor). Each donor had 3 samples treated in hypoxia and 3 in normoxia. In each oxygen tension, the treatments were Dynamic Compression, Static Compression, or Baseline. Each individual sample came from pooled equal masses of RNA from 3-4 biological replicates in the same condition from the same donor.