Simulated microgravity recapitulates early molecular events and sex differences of knee osteoarthritis

This study aims to establish an osteoarthritis (OA)-like phenotype in human meniscus models under SMG conditions and assess whether sex-dependent expression patterns indicative of knee OA (KOA) are present under short-term SMG. Cell cultures were maintained on human matrix coated surface to maintain original phenotype. Primary fibrochondrocytes obtained from six donors (three male and three female) without KOA were cultured on human matrix coated surface and used to engineer human meniscus constructs. The constructs were cultured under normal gravity and simulated microgravity for seven days, and samples were collected on days 0, 1, 3, and 7. The expression levels of selected markers and whole transcriptome profile were assessed using RT-qPCR and RNA sequencing.

本研究旨在在模拟微重力（SMG）条件下的人类半月板模型中构建类骨关节炎（OA）表型，并评估短期SMG条件下是否存在提示膝骨关节炎（KOA）的性别依赖性基因表达模式。为维持细胞原始表型，实验将细胞培养于包被人类细胞外基质的表面。从6名无膝骨关节炎（KOA）的供者（3名男性、3名女性）中分离得到原代纤维软骨细胞，将其培养于包被人类细胞外基质的表面，用于构建人类半月板组织工程构建体。将上述构建体分别置于正常重力及模拟微重力环境中培养7天，并于第0、1、3及7天收集样本。采用逆转录实时定量聚合酶链反应（RT-qPCR）及RNA测序（RNA sequencing）对选定标志物的表达水平及全转录组表达谱进行检测分析。