ObjectiveTo date, exhaustive gene expression analyses of chondrocytes in hip osteoarthritis (OA) have yielded specific gene expression patterns. No study has reported on the exhaustive transcriptome of secondary hip OA based on acetabular dysplasia in a Japanese population, while previous reports have focused on primary or idiopathic hip OA in Caucasian populations. This study aims to search for specific gene expression patterns of secondary hip OA chondrocytes by transcriptome analysis.DesignHuman articular cartilage was obtained from femoral heads following hemiarthroplasty for femoral neck fracture (N = 8; non-OA) and total hip arthroplasty for secondary hip OA (N = 12). Total RNA was extracted from the articular cartilage and submitted for microarray analysis. The obtained data were used to perform gene expression analysis, GO enrichment analysis and pathway analysis and were compared with data from primary hip OA in Caucasian populations in the literature.ResultsWe identified 888 upregulated (fold change: FC ≥ 2) and 732 downregulated (FC ≤ 0.5) genes in hip OA versus non-OA chondrocytes, respectively. Only 10% of upregulated genes were common between the secondary and primary OA. The newly found genes prominently overexpressed in the secondary hip OA chondrocytes were DPT, IGFBP7, and KLF2. Pathway analysis revealed extracellular matrix (ECM)-receptor interaction as an OA-related pathway, which was similar to previous reports in primary hip OA.ConclusionsThis is the first study to report the genome-wide transcriptome of secondary hip OA chondrocytes and demonstrates new potential OA-related genes. Gene expression patterns were different between secondary and primary hip OA, although the results of pathway and functional analysis were similar.

Case-control study, Level III.

The angle between FA and MA in the sagittal plane increased in patients with large medial tibial torsion.

This study examined the association between developmental dysplasia of the hip (DDH) and disease-associated loci in a Japanese cohort. A genome-wide association study (GWAS) of 238 Japanese patients with DDH and 2044 healthy individuals was performed. As a replicate, GWAS was also conducted on the UK Biobank data with 3315 cases and matched 74,038 controls. Gene set enrichment analyses (GSEAs) of both the genetics and transcriptome of DDH were performed. Transcriptome analysis of cartilage specimens from DDH-associated osteoarthritis and femoral neck fractures was performed as a control. Most of the lead variants were very low-frequency ones in the UK, and variants in the Japanese GWAS could not be replicated with the UK GWAS. We assigned DDH-related candidate variants to 42 and 81 genes from the Japanese and UK GWASs, respectively, using functional mapping and annotation. GSEA of gene ontology, disease ontology, and canonical pathways identified the most enriched pathway to be the ferroptosis signaling pathway, both in the Japanese gene set as well as the Japanese and UK merged set. Transcriptome GSEA also identified significant downregulation of genes in the ferroptosis signaling pathway. Thus, the ferroptosis signaling pathway may be associated with the pathogenic mechanism of DDH.

No abstract