Zhou Tingting, Ma Shiqiang, Zhao Yunchao, Guo Donghui, Wang Hengjun, Kuang Mingjie, Li Xiaoming
Department of Orthopedics, Traditional Chinese Medicine-Western Medicine Hospital of Cangzhou City, Cangzhou, China.
Hebei Key Laboratory of Integrated Traditional and Western Medicine in Osteoarthrosis Research (Preparing), Cangzhou, China.
Front Genet. 2022 Sep 30;13:918379. doi: 10.3389/fgene.2022.918379. eCollection 2022.
Alcohol-induced osteonecrosis of the femoral head (AIONFH) is a complicated refractory bone disease seen in the clinic. The pathogenesis of AIONFH is still controversial. Extrachromosomal circular DNA (eccDNA) elements have been indicated ubiquitously exist in eukaryotic genomes. However, the characteristics and biological functions of eccDNAs remain unclear in AIONFH. In this study, eccDNAs from AIONFH samples ( = 7) and fracture of femoral neck samples as a control ( = 7) were purified by removing linear DNA and rolling circle amplification. High-throughput sequencing and bioinformatics analysis were performed to study the characterization and biofunction of eccDNAs. We identified more than 600,000 unique eccDNAs. The number of detected eccDNAs in AIONFH was less than that in the control, and eccDNA formation may be related to transcription or other characteristics of coding genes. The eccDNA lengths are mainly distributed between 0.1 kb and 1 kb, with a major peak in 0.358 kb. The bioinformatic analysis showed that 25 significant genes were detected, including , , , and , which contributed to regulating bone formation. GO and KEGG analyses suggested that the related genes derived from exons mainly affected metabolic processes and signal transduction, and bone metabolism-related pathways, such as the pathway and pathway, were enriched. EccDNAs in AIONFH are common and may play an important role in pathogenesis by regulating bone metabolism.
酒精性股骨头坏死（AIONFH）是临床上一种复杂难治的骨病。AIONFH的发病机制仍存在争议。已有研究表明，染色体外环状DNA（eccDNA）元件普遍存在于真核生物基因组中。然而，在AIONFH中，eccDNA的特征和生物学功能仍不清楚。在本研究中，通过去除线性DNA和滚环扩增，从AIONFH样本（n = 7）和作为对照的股骨颈骨折样本（n = 7）中纯化出eccDNA。采用高通量测序和生物信息学分析来研究eccDNA的特征和生物功能。我们鉴定出了超过60万个独特的eccDNA。AIONFH中检测到的eccDNA数量少于对照组，且eccDNA的形成可能与编码基因的转录或其他特征有关。eccDNA长度主要分布在0.1 kb至1 kb之间，主峰在0.358 kb处。生物信息学分析表明，检测到25个显著基因，包括COL1A1、COL1A2、SPP1和IBSP，它们有助于调节骨形成。GO和KEGG分析表明，来源于外显子的相关基因主要影响代谢过程和信号转导，并且富集了骨代谢相关途径，如TGF-β信号通路和Wnt信号通路。AIONFH中的eccDNA普遍存在，可能通过调节骨代谢在发病机制中发挥重要作用。
