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
Department of Surgery, Divisions of Orthopaedic Surgery and Surgical Research, Faculty of Medicine & Dentistry, University of Alberta, Li Ka Shing Centre for Health Research Innovation, Edmonton, AB, Canada.
Graduate Program of Rehabilitation Sciences, University of Brasília (UnB), Brasília, Distrito Federal, Brazil.
J Tissue Eng. 2021 Feb 6;12:2041731421990842. doi: 10.1177/2041731421990842. eCollection 2021 Jan-Dec.
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) conditions with supplemented TGF-β3. Tissues experienced a delayed 24h hypoxia treatment (HYP, 3% O) 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 and . 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.
本研究使用模型系统研究半月板纤维软骨细胞(MFCs)对膝关节中低氧和机械负荷信号的转录组反应。我们假设短期暴露于联合治疗会促进支持内侧半月板组织形成的基质形成表型。在补充了转化生长因子-β3的常氧(NRX,20% O)条件下,将胶原支架上的人MFCs刺激6周以形成纤维软骨。组织经历延迟24小时的低氧处理(HYP,3% O),然后在30%至40%应变之间进行5分钟的动态压缩(DC)。延迟低氧诱导了透明软骨基质标志物的合成代谢和抗分解代谢表达谱,而动态压缩诱导了炎症性基质重塑反应以及[此处原文缺失两个基因名称]的上调。有41个基因受低氧和动态压缩共同调控。总体而言,联合治疗支持一种独特的基因表达谱,有利于内侧半月板基质的透明软骨方面和基质重塑。