Novel role of miR‐181a in cartilage metabolism

Abstract

Micro RNA (miRNA) is a small non-coding post-transcriptional RNA regulator that is involved in a variety of biological events. In order to specify the role of miRNAs in cartilage metabolism, we comparatively analyzed the expression profile of known miRNAs in chicken sternum chondrocytes representing early and late differentiation stages. Interestingly, none of the miRNAs displaying strong expression levels showed remarkable changes along with differentiation, suggesting their roles in maintaining the homeostasis rather than cytodifferentiation of chondrocytes. Among these miRNAs, miR-181a, which is known to play critical roles in a number of tissues, was selected and was further characterized. Human microarray analysis revealed remarkably stronger expression of miR-181a in human HCS-2/8 cells, which strongly maintained a chondrocytic phenotype, than in HeLa cells, indicating its significant role in chondrocytes. Indeed, subsequent investigation indicated that miR-181a repressed the expression of two genes involved in cartilage development. One was CCN family member 1 (CCN1), which promotes chondrogenesis; and the other, the gene encoding the core protein of aggrecan, a major cartilaginous proteoglycan, aggrecan. Based on these findings, negative feedback system via miR-181a to conserve the integrity of the cartilaginous phenotype may be proposed.

Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet cartilage degeneration

“…However, recent studies performed in chondrocytes isolated from chicken sternal cartilage show that miR-181a reduces the expression of COL2A1 (22). Gabler et al showed that the expression of miR-181a is increased during hypertrophic chondrocyte differentiation in human mesenchymal stromal cells treated with transforming growth factor-β (23).…”

The CCN family acting throughout the body: recent research developments

“…In chicken CCN1, a coding segment on the mRNA supports the expression of CCN1 by facilitating ribosomal recruitment (79). Another report suggests that miR-181a represses CCN1 at a posttranscriptional stage of gene expression, which is mediated by a region outside of the 3′-UTR (80). Progress in similar research on other CCN family members will clarify the solid contribution of miRNAs to the regulation of the CCN family genes.…”

MicroRNAs involved in bone formation

“…Mir-181a represses expression of Ccna2 (encoding for cyclin A2) and Acan . The regulation of these chondrocyte genes by miR-181a may act as a negative feedback for cartilage homeostasis [47]. Another study in chicken cells found that miR-221 was increased upon inhibition of chondrocyte differentiation [48].…”