Department of Mechanical Engineering, University of Delaware, Newark, DE, United States.
Center for Bioinformatics and Computational Biology, University of Delaware, Newark, DE, United States.
Sci Rep. 2019 Jan 14;9(1):93. doi: 10.1038/s41598-018-36500-2.
Traumatic joint injuries often result in elevated proinflammatory cytokine (such as IL-1β) levels in the joint cavity, which can increase the catabolic activities of chondrocytes and damage cartilage. This study investigated the early genetic responses of healthy in situ chondrocytes under IL-1β attack with a focus on cell cycle and calcium signaling pathways. RNA sequencing analysis identified 2,232 significantly changed genes by IL-1β, with 1,259 upregulated and 973 downregulated genes. Catabolic genes related to ECM degeneration were promoted by IL-1β, consistent with our observations of matrix protein loss and mechanical property decrease during 24-day in vitro culture of cartilage explants. IL-1β altered the cell cycle (108 genes) and Rho GTPases signaling (72 genes) in chondrocytes, while chondrocyte phenotypic shift was observed with histology, cell volume measurement, and MTT assay. IL-1β inhibited the spontaneous calcium signaling in chondrocytes, a fundamental signaling event in chondrocyte metabolic activities. The expression of 24 genes from 6 calcium-signaling related pathways were changed by IL-1β exposure. This study provided a comprehensive list of differentially expressed genes of healthy in situ chondrocytes in response to IL-1β attack, which represents a useful reference to verify and guide future cartilage studies related to the acute inflammation after joint trauma.
创伤性关节损伤常导致关节腔内促炎细胞因子（如 IL-1β）水平升高，这会增加软骨细胞的分解代谢活性并损害软骨。本研究通过 IL-1β 攻击，研究了健康原位软骨细胞的早期遗传反应，重点关注细胞周期和钙信号通路。RNA 测序分析鉴定出 2232 个受 IL-1β显著影响的基因，其中 1259 个上调，973 个下调。与我们在软骨外植体 24 天体外培养期间观察到的基质蛋白丢失和机械性能下降一致，IL-1β 促进了与 ECM 降解相关的分解代谢基因。IL-1β 改变了软骨细胞中的细胞周期（108 个基因）和 Rho GTPases 信号（72 个基因），而组织学、细胞体积测量和 MTT 测定观察到软骨细胞表型转变。IL-1β 抑制了软骨细胞中自发的钙信号，这是软骨细胞代谢活动中的基本信号事件。6 条钙信号相关途径中的 24 个基因的表达受 IL-1β 暴露的影响。本研究提供了健康原位软骨细胞对 IL-1β 攻击反应的差异表达基因的综合列表，这为验证和指导未来与关节创伤后急性炎症相关的软骨研究提供了有用的参考。
