The mechanisms of myricetin and quercetin in regulating miRNA-140 and MMP/TIMP signaling pathway in osteoarthritis treatment.

OBJECTIVES

This study investigates the combined therapeutic effects of myricetin (Myr) and quercetin (Que) on miRNA-140 regulation and the MMP/TIMP signaling pathway involved in cartilage matrix remodeling in osteoarthritis (OA).

METHODS

In-vitro OA models were established using IL-1β-treated CHON-001 human chondrocytes, while in-vivo OA models were induced by monosodium iodoacetate (MIA) injection in male SD rats. Myr (10 μM in-vitro; 25 mg/kg in-vivo), Que (50 μM in-vitro; 10 mg/kg in-vivo), or their combination was administered. CCK-8 and TUNEL assays assessed cell viability and apoptosis, while qRT-PCR evaluated miRNA-140 expression. Western blot detected MMP/TIMP proteins and ELISA quantified IL-1β, TNF-α, IL-6 and PGE2 in supernatant and serum samples.

RESULTS

Myr and Que individually improved chondrocyte viability and reduced apoptosis, with the combination showing the strongest effect in-vitro. These effects were confirmed in-vivo, where combined treatment alleviated cartilage damage, restored miRNA-140 expression, suppressed MMP-3 and MMP-13 and upregulated TIMP-1 and TIMP-3. TNF-α levels were significantly reduced by co-treatment, while IL-1β and IL-6 showed moderate decreases, indicating synergistic anti-inflammatory and cartilage-protective effects.

CONCLUSION

These findings suggest a miRNA-140-associated regulatory relationship between myricetin/quercetin treatment and MMP/TIMP pathway modulation.