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

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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.
社団法人日本薬理学会の論文

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

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