Aucubin inhibits IL-1β- or TNF-α-induced extracellular matrix degradation in nucleus pulposus cell through blocking...

In intervertebral disc degeneration (IDD), increased proinflammatory molecules secreted by human nucleus pulposus cells (HNPCs) could promote the expression of extracellular matrix (ECM)-degrading enzymes. IDD could be affected by both genetic and environmental factors, including microRNAs (miRNAs). Aucubin, the active ingredient of a traditional Chinese medicine herb Du Zhong, has been reported to promote osteogenic differentiation; however, the role of aucubin in IDD and the underlying mechanism remain unclear. Herein, we evaluated the effect of aucubin on TNF-α- or IL-1β-induced ECM degradation in HNPCs. By using online tools, miR-140 was selected as a candidate miRNA that is related to TNF-α or IL-1β signaling. Overexpression of miR-140 enhanced the effect of aucubin on ECM degradation. Moreover, cAMP responsive element binding protein 1 (CREB1), a major transcriptional factor in immune-related signaling, was a direct downstream target of miR-140. CREB1 knockdown mimicked the function of miR-140 overexpression on ECM degradation. In summary, aucubin might ameliorate IL-1β- or TNF-α-induced ECM degradation in HNPCs through regulating miR-140/CREB1.