MicroRNA‐199a‐3p, microRNA‐193b, and microRNA‐320c are correlated to aging and regulate human cartilage metabolism

Abstract

MicroRNAs (miRNAs) are small RNAs of $22 base pairs that regulate gene expression. We harvested cartilage tissue from patients with polydactylism, anterior cruciate ligament injury, and osteoarthritis undergoing total knee arthroplasty and used microarrays to identify miRNAs whose expression is upregulated or downregulated with age. The results were assessed by real-time PCR and MTT assay in a mimic group, in which synthetic double-stranded RNA from the isolated miRNA was transfected to upregulate expression, and in an inhibitor group, in which the miRNA was bound specifically to downregulate expression. The expression of two miRNAs (miR-199a-3p and miR-193b) was upregulated with age and that of one miRNA (miR-320c) was downregulated with age. A real-time PCR assay showed that type 2 collagen, aggrecan, and SOX9 expression were downregulated in the miR-199a-3p mimic group but was upregulated in the inhibitor group. Similar results were observed for miR-193b. By contrast, ADAMTS5 expression was downregulated in the miR-320c mimic group and upregulated in the inhibitor group. Cell proliferative activity was upregulated significantly in the miR-193b inhibitor group compared with the control group. We believe that miR-199a-3p and miR-193b are involved in the senescence of chondrocytes, and miR-320c is involved in the juvenile properties of chondrocytes. ß

Comparative study of microRNA profiling in keloid fibroblast and annotation of differential expressed microRNAs

“…Some miRNAs identified in this study have been shown to play important roles in biological procedures of cellular mechanisms [43]. For example, miR-152, miR-23, miR-30a, and miR-31 show increased levels in tissue samples diagnosed with lung cancer [44], while the expression levels of miRNA-320c are correlated with aging, and miRNA-320c can regulate human cartilage metabolism [45]. Recent evidence has shown that miR-152 is required for proper cell cycle progression and plays critical roles in the S-phase and G2/M-phase cell cycle progression of diploid fibroblasts.…”

Intra-articular Delivery of Antago-miR-483-5p Inhibits Osteoarthritis by Modulating Matrilin 3 and Tissue Inhibitor of Metalloproteinase 2

“…6 The emerging role of miRNAs in OA is evident from studies comparing miRNA expression in both OA and normal articular tissues. miRNAs, including miR-140, 7,8 miR-320c, 9 miR-125b, 10 miR-27b, 11 miR-194, 12 miR-199a*, 13 miR-34a, 14 and miR-146a, 15 are implicated in various aspects of OA pathology, including regulating proteolytic enzymes, chondrocyte metabolism, and cartilage homeostasis and responding to the inflammatory microenvironment. Therefore, identification of the miRNAs regulatory network involved in OA is crucial for understanding its pathogenesis.…”

Significance of Epigenetic Landscape in Cartilage Regeneration from the Cartilage Development and Pathology Perspective

“…It was also found in human diploid fibroblasts that miR-519 triggered replicative senescence by repressing an RNA-binding protein known as HuR [58]. Finally, miR-199a-3p, miR-193b, and miR-320c were specifically identified to correlate to the senescence of chondrocytes [59]. The changes in miRNAs may lead to interactions with methylation and histone modifications of target genes, consequently influencing human MSC selfrenewal and differentiation [60].…”