Sakai Eiko, Tsukuba Takayuki
Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1, Sakamoto, Nagasaki 852-8588, Japan.
Antioxidants (Basel). 2024 Dec 20;13(12):1575. doi: 10.3390/antiox13121575.
Although osteoclasts play crucial roles in the skeletal system, the mechanisms that underlie oxidative stress during osteoclastogenesis remain unclear. The transcription factor Nrf2 and its suppressor, Keap1, function as central mediators of oxidative stress. To further elucidate the function of Nrf2/Keap1-mediated oxidative stress regulation in osteoclastogenesis, DNA microarray analysis was conducted in this study using wild-type (WT), knockout ( KO), and knockout ( KO) osteoclasts. Principal component analysis showed that 403 genes, including , , and , were upregulated in KO compared with WT osteoclasts, whereas 24 genes, including , , and , were upregulated in KO compared with WT osteoclasts. Moreover, 683 genes, including , , and , were upregulated in KO cells compared to KO cells. Functional analysis by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed upregulated genes in KO osteoclasts were mostly enriched in oxidative phosphorylation. Furthermore, GeneMANIA predicted the protein-protein interaction network of novel molecules such as Rufy4 from genes upregulated in KO osteoclasts. Understanding the complex interactions between these molecules may pave the way for developing promising therapeutic strategies against bone metabolic diseases caused by increased osteoclast differentiation under oxidative stress.
尽管破骨细胞在骨骼系统中发挥着关键作用，但破骨细胞生成过程中氧化应激的潜在机制仍不清楚。转录因子Nrf2及其抑制因子Keap1作为氧化应激的核心介质发挥作用。为了进一步阐明Nrf2/Keap1介导的氧化应激调节在破骨细胞生成中的功能，本研究使用野生型（WT）、敲除（KO）和敲除（KO）破骨细胞进行了DNA微阵列分析。主成分分析表明，与WT破骨细胞相比，KO中有403个基因上调，包括、和，而与WT破骨细胞相比，KO中有24个基因上调，包括、和。此外，与KO细胞相比，KO细胞中有683个基因上调，包括、和。通过基因本体论和京都基因与基因组百科全书通路分析进行的功能分析表明，KO破骨细胞中上调的基因大多富集在氧化磷酸化中。此外，GeneMANIA预测了KO破骨细胞中上调基因如Rufy4等新分子的蛋白质-蛋白质相互作用网络。了解这些分子之间的复杂相互作用可能为开发针对氧化应激下破骨细胞分化增加所导致的骨代谢疾病的有前景的治疗策略铺平道路。
