Abstract
BackgroundOsteoarthritis (OA) is a chronic degenerative joint disease and the most frequent type of arthritis. This study aimed to identify the key miRNAs and genes associated with OA progression.MethodsThe GSE105027 (microRNA [miRNA/miR] expression profile; 12 OA samples and 12 normal samples) and GSE48556 (messenger RNA [mRNA] expression profile; 106 OA samples and 33 normal samples) datasets were selected from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEMs) were analyzed using the limma and ROCR packages in R, respectively. The target genes that negatively correlated with the DEMs were predicted, followed by functional enrichment analysis and construction of the miRNA-gene and miRNA-transcription factor (TF)-gene regulatory networks. Additionally, key miRNAs and genes were screened, and their expression levels were verified by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsA total of 1696 DEGs (739 upregulated and 957 downregulated) and 108 DEMs (56 upregulated and 52 downregulated) were identified in the OA samples. Furthermore, 56 target genes that negatively correlated with the DEMs were predicted and found to be enriched in three functional terms (e.g., positive regulation of intracellular protein transport) and three pathways (e.g., human cytomegalovirus infection). In addition, three key miRNAs (miR-98-5p, miR-7-5p, and miR-182-5p) and six key genes (murine double minute 2, MDM2; glycogen synthase kinase 3-beta, GSK3B; transmembrane P24-trafficking protein 10, TMED10; DDB1 and CUL4-associated factor 12, DCAF12; caspase 3, CASP3; and ring finger protein 44, RNF44) were screened, among which the miR-7-5p → TMED10/DCAF12, miR-98-5p → CASP3/RNF44, and miR-182-5p → GSK3B pairs were observed in the regulatory network. Moreover, the expression levels of TMED10, miR-7-5p, CASP3, miR-98-5p, GSK3B, and miR-182-5p showed a negative correlation with qRT-PCR verification.ConclusionMiR-98-5p, miR-7-5p, miR-182-5p, MDM2, GSK3B, TMED10, DCAF12, CASP3, and RNF44 may play critical roles in OA progression.
Highlights
Osteoarthritis (OA) is a chronic degenerative joint disease and the most frequent type of arthritis
The P value of mRNA differential analysis was corrected for the false discovery rate (FDR), and genes with a FDR < 0.05 were regarded as Differentially expressed genes (DEGs)
Enrichment analysis For the 56 target genes that were negatively correlated with 12 differentially expressed miRNAs (DEMs), GO_BP and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out
Summary
Osteoarthritis (OA) is a chronic degenerative joint disease and the most frequent type of arthritis. As a chronic degenerative joint disease, osteoarthritis (OA) is induced by the destruction of articular cartilage and bone tissue [1]. The most common symptoms of OA include joint pain, joint swelling, stiffness, and limited motion range [2]. The therapeutic options for OA include reduction of joint stress, exercise, pain medications, and support groups [5]. OA is the most frequent type of arthritis and affects approximately 237 million people globally [6]. Exploring the mechanisms of OA is necessary in order to improve its diagnosis and therapeutic options
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