miR9 inhibits 6-mer HA-induced cytokine production and apoptosis in human chondrocytes by reducing NF-kB activation

The present study aimed to investigate the expression of miR9 and its correlation with cytokines, proteolytic enzymes and apoptosis in an experimental model of 6-mer HA induced inflammation in human chondrocytes.Human articular chondrocytes, transfected with a miR-9 mimic and miR-9 inhibitor, were stimulated with 6mer HA in presence/absence of a specific NF-kB inhibitor.6-mer HA induced a significant increase of TLR-4, CD44, IL-8, IL-18, MMP-9, ADAMTS-5, BAX and BCL-2 mRNAs expression and the related proteins, as well as NF-kB activation, associated with a significant up regulation of miR-9. In chondrocytes transfected with the miR-9 mimic before 6-mer HA treatment we found a decrease of such inflammatory cytokines, metalloproteases and pro-apoptotic molecules, while we found them increased in chondrocytes transfected with the miR9 inhibitor before 6-mer HA stimulation. The activities of TLR-4 and CD44, up regulated by 6-mer HA, were not modified by miR9 mimic/inhibitor, while the NF-kB activation was significantly affected.We suggested that the up regulation of miR9, induced by 6-mer HA, could be a cellular attempt to limit cell damage during inflammation.

Automated summary

This study investigated the expression of miR9 and its relationship with cytokines, proteolytic enzymes, and apoptosis in an experimental model of 6mer HA-induced inflammation in human chondrocytes. The researchers found that 6mer HA stimulation significantly increased the expression of TLR-4, CD44, IL-8, IL-18, MMP-9, ADAMTS-5, BAX, and BCL-2 mRNAs, as well as related proteins and NF-kB activation. Upregulation of miR9 was also observed in response to 6mer HA. Transfection of chondrocytes with miR-9 mimic decreased the expression of inflammatory cytokines, metalloproteases, and pro-apoptotic molecules, while transfection with miR9 inhibitor increased their expression. However, the activities of TLR-4 and CD44 were not affected by miR9 mimic/inhibitor, but NF-kB activation was significantly affected.