Luteolin downregulates IL-1β-induced MMP-9 and -13 expressions in osteoblasts via inhibition of ERK signalling pathway

Abstract

The inhibitory effect of four structurally related flavonoids, apigenin, baicalein, luteolin and quercetin on the matrix metalloproteinase (MMP)-9 and -13 expressions in osteoblasts was investigated. Treatment with IL-1β induced both MMP-9 and -13 mRNA expressions as measured by quantitative real-time PCR. Luteolin and apigenin decreased IL-1β-induced MMP-9 and -13 mRNA expressions, whereas baicalein and quercetin showed little effects. Related to signalling, treatment with IL-1β induced ERK phosphorylation as measured by Western blotting. Further studies showed that transfection with a constitutively active form of the Ras protein (Ras^V12) induced stronger ERK phosphorylation and upregulated MMP-9 and -13 mRNA expressions. However, transfection with a dominant-negative form of the Ras protein (Ras^N17) inhibited the ERK activation and MMP-9 and -13 mRNA expressions induced by IL-1β, which supported the involvement of ERK signalling in IL-1β-induced MMP-9 and -13 expressions. Treatment with luteolin effectively inhibited the IL-1β-induced ERK activation in dose-dependent manner. Taken together, luteolin might inhibit IL-1β-induced MMP-9 and -13 expressions, in part, via inhibition of ERK signalling.

Keywords::

• Matrix metalloprotenase
• flavonoid
• osteoblasts
• luteolin
• extracellular signal-regulated kinase

Acknowledgment

This work was supported by the Medical Research Center program through the National Research Foundation of Korea (2010-0029480).

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.