Integrative Analysis of MicroRNA and mRNA Sequencing Data Identifies Novel Candidate Genes and Pathways for Developmental Dysplasia of Hip

Objective: Our aim is to explore the candidate pathogenesis genes and pathways of developmental dysplasia of hip (DDH). Design: 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. Results: 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 VWA1, TMEM119, and SCUBE3. Further gene ontology enrichment analysis detected 111 candidate terms for DDH, such as skeletal system morphogenesis (P = 4.92 × 10⁻⁵) and skeletal system development (P = 8.85 × 10⁻⁵). Pathway enrichment analysis identified 14 candidate pathways for DDH, such as Hedgehog signaling pathway (P = 4.29 × 10⁻⁵) and Wnt signaling pathway (P = 4.42 × 10⁻²). Among the identified DDH associated candidate genes, we also found some genes were detected in hip OA including EFNA1 and VWA1. Conclusions: We identified multiple novel candidate genes and pathways for DDH, providing novel clues for understanding the molecular mechanism of DDH.