Table1_Unbiased comparison and modularization identify time-related transcriptomic reprogramming in exercised rat cartilage: Integrated data mining and experimental validation.XLSX

Exercise is indispensable for maintaining cartilage integrity in healthy joints and remains a recommendation for knee osteoarthritis. Although the effects of exercise on cartilage have been implied, the detailed mechanisms, such as the effect of exercise time which is important for exercise prescription, remain elusive. In this study, bioinformatic analyses, including unbiased comparisons and modularization, were performed on the transcriptomic data of rat cartilage to identify the time-related genes and signaling pathways. We found that exercise had a notable effect on cartilage transcriptome. Exercise prominently suppressed the genes related to cell division, hypertrophy, catabolism, inflammation, and immune response. The downregulated genes were more prominent and stable over time than the upregulated genes. Although exercise time did not prominently contribute to the effects of exercise, it was a factor related to a batch of cellular functions and signaling pathways, such as extracellular matrix (ECM) homeostasis and cellular response to growth factors and stress. Two clusters of genes, including early and late response genes, were identified according to the expression pattern over time. ECM organization, BMP signaling, and PI3K-Akt signaling were early responsive in the exercise duration. Moreover, time-related signaling pathways, such as inositol phosphate metabolism, nicotinate/nicotinamide metabolism, cell cycle, and Fc epsilon RI signaling pathway, were identified by unbiased mapping and polarization of the highly time-correlated genes. Immunohistochemistry staining showed that Egfr was a late response gene that increased on day 15 of exercise. This study elucidated time-related transcriptomic reprogramming induced by exercise in cartilage, advancing the understanding of cartilage homeostasis.

运动对于维持健康关节内软骨（cartilage）的完整性不可或缺，同时也是膝骨关节炎（knee osteoarthritis）的临床推荐干预手段。尽管运动对软骨的作用已被初步揭示，但其背后的具体调控机制仍不明晰——其中运动时长作为运动处方（exercise prescription）制定的关键参数，其具体影响尚未得到充分阐释。本研究针对大鼠软骨转录组数据（transcriptomic data）开展生物信息学分析，包括无偏比较与模块化分析，旨在筛选与运动时长相关的基因及信号通路（signaling pathways）。研究结果显示，运动对软骨转录组具有显著调控作用。运动可显著抑制与细胞分裂、软骨细胞肥大、分解代谢、炎症及免疫应答相关的基因表达。相较于上调基因，下调基因的表达变化更为显著且随时间推移更具稳定性。尽管运动时长并未显著影响运动的整体调控效果，但其与诸多细胞功能及信号通路密切相关，例如细胞外基质（extracellular matrix, ECM）稳态、细胞对生长因子与应激的应答反应。根据基因随时间的表达模式，本研究筛选出两类基因簇：早期应答基因与晚期应答基因。细胞外基质组装、骨形态发生蛋白信号通路（BMP signaling）及磷脂酰肌醇3-激酶-蛋白激酶B信号通路（PI3K-Akt signaling）在运动早期即产生应答。此外，通过对高时间相关性基因进行无偏映射与极化分析，本研究还筛选出与运动时长相关的信号通路，包括肌醇磷酸代谢、烟酸/烟酰胺代谢、细胞周期及FcεRI信号通路（Fc epsilon RI signaling pathway）。免疫组织化学染色结果显示，表皮生长因子受体（Egfr）是一种晚期应答基因，其表达在运动第15天时显著上调。本研究阐明了运动诱导的软骨时间依赖性转录组重编程过程，加深了人们对软骨稳态的认知。