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

• Published in: Journal of tissue engineering Vol. 12; p. 2041731421990842
• Main Authors: Szojka, Alexander RA, Marqueti, Rita de Cássia, Li, David Xinzheyang, Molter, Clayton W, Liang, Yan, Kunze, Melanie, Mulet-Sierra, Aillette, Jomha, Nadr M, Adesida, Adetola B
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 2021; Sage Publications Ltd; SAGE Publishing
• Subjects: Cartilage; Collagen; Collagen (type I); Combined treatment; Compression; Gene expression; Hypoxia; Inflammation; Mechanical loading; Meniscus; Original; Phenotypes; Sox9 protein; Transcriptomes; mechanical loading; hypoxia; Human engineered meniscus; transcriptome; dynamic compression
• ISSN: 2041-7314; 2041-7314
• DOI: 10.1177/2041731421990842

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% O2) conditions with supplemented TGF-β3. Tissues experienced a delayed 24h hypoxia treatment (HYP, 3% O2) 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.