Effects of flavonoids on matrix metalloproteinase-13 expression of interleukin-1β-treated articular chondrocytes and their cellular mechanisms: Inhibition of c-Fos/AP-1 and JAK/STAT signaling pathways

To identify the therapeutic potential for cartilage degradation and its action mechanisms,the effects of naturally-occurring flavonoids on matrix metalloproteinase-13 (mmp-13) induction were examined in the human chondrocyte cell line sw1353. flavones including apigenin and wogonin strongly inhibited mmp-13 induction in interleukin (il)-1β-treated sw1353 cells,while flavonols such as kaempferol,quercetin,and flavanone (naringenin) did not at 5 - 25 μm. apigenin and wogonin primarily inhibit mmp-13 by blocking the c-fos / activator protein-1 (ap-1) and janus kinase 2 (jak2) / signal transducer and activator of transcription 1/2 (stat1/2) pathways,but not nuclear factor-κb (nf-κb) signaling. apigenin was also shown to inhibit extracellular matrix degradation in rabbit cartilage culture. the following study using some synthetic flavones demonstrated that a-ring c-5,7-dihydroxyl and b-ring dihydroxyl substitution at c-2,3,c-2,4,or c-3,4 are important for the suppression of mmp-13 expression. among these flavones,2?,3?,5,7- tetrahydroxyflavone also inhibited both the c-fos/ap-1 and stat1/2 pathways. taken together,these results indicate that certain flavonoids,especially flavones,inhibit mmp-13 expression in il-1β-treated chondrocytes,at least in part,by suppressing the c-fos/ap-1 and jak2/stat1/2 pathways. furthermore,these findings suggest that some flavonoids have the potential for protecting against collagen matrix breakdown in the cartilage of diseased tissues such as those found in arthritic disorders. © the japanese pharmacological society.