Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, People's Republic of China.
Department of Joint Surgery, Xi'an Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, People's Republic of China.
Cartilage. 2021 Dec;13(2_suppl):1618S-1626S. doi: 10.1177/1947603521990859. Epub 2021 Feb 1.
Our aim is to explore the candidate pathogenesis genes and pathways of developmental dysplasia of hip (DDH).
Proliferating primary chondrocytes from hip cartilage were used for total RNA extraction including 5 DDH patients and 5 neck of femur fracture (NOF) subjects. Genome-wide mRNA and microRNA (miRNA) were then sequenced on the Illumina platform (HiSeq2500). Limma package was used for difference analysis of mRNA expression profiles. edgeR was used for difference analysis of miRNA expression profiles. miRanda was used to predict miRNA-target genes. The overlapped DDH associated genes identified by mRNA and miRNA integrative analysis were further compared with the differently expressed genes in hip osteoarthritis (OA) cartilage.
Differential expression analysis identified 1,833 differently expressed mRNA and 186 differently expressed miRNA for DDH. Integrative analysis of mRNA and miRNA expression profiles identified 175 overlapped candidate genes (differentially expressed genes, DEGs) for DDH, such as , , and . Further gene ontology enrichment analysis detected 111 candidate terms for DDH, such as skeletal system morphogenesis ( = 4.92 × 10) and skeletal system development ( = 8.85 × 10). Pathway enrichment analysis identified 14 candidate pathways for DDH, such as Hedgehog signaling pathway ( = 4.29 × 10) and Wnt signaling pathway ( = 4.42 × 10). Among the identified DDH associated candidate genes, we also found some genes were detected in hip OA including and .
We identified multiple novel candidate genes and pathways for DDH, providing novel clues for understanding the molecular mechanism of DDH.
探讨发育性髋关节发育不良（DDH）的候选发病机制基因和途径。
从髋关节软骨中提取增殖的原代软骨细胞，包括 5 例 DDH 患者和 5 例股骨颈骨折（NOF）患者的总 RNA。然后在 Illumina 平台（HiSeq2500）上对全基因组 mRNA 和 microRNA（miRNA）进行测序。使用 Limma 包对 mRNA 表达谱进行差异分析。使用 edgeR 对 miRNA 表达谱进行差异分析。使用 miRanda 预测 miRNA 靶基因。mRNA 和 miRNA 整合分析鉴定的重叠 DDH 相关基因与髋骨关节炎（OA）软骨中差异表达的基因进一步比较。
差异表达分析确定了 1833 个差异表达的 mRNA 和 186 个差异表达的 miRNA 用于 DDH。mRNA 和 miRNA 表达谱的综合分析确定了 175 个重叠的 DDH 候选基因（差异表达基因，DEGs），如、和。进一步的基因本体富集分析检测到 111 个 DDH 候选术语，如骨骼系统形态发生（= 4.92×10）和骨骼系统发育（= 8.85×10）。途径富集分析确定了 14 个 DDH 候选途径，如 Hedgehog 信号通路（= 4.29×10）和 Wnt 信号通路（= 4.42×10）。在鉴定的 DDH 相关候选基因中，我们还发现了一些在髋 OA 中检测到的基因，包括和。
我们确定了多个用于 DDH 的新候选基因和途径，为了解 DDH 的分子机制提供了新的线索。
