Tangeretin suppresses osteoarthritis progression via the Nrf2/NF-κB and MAPK/NF-κB signaling pathways

Area of Science:

• Biochemistry
• Pharmacology
• Immunology

Background:

• Osteoarthritis (OA) is a widespread degenerative joint disease marked by extracellular matrix (ECM) breakdown and inflammation.
• Tangeretin, a flavonoid, possesses known anti-inflammatory properties, but its role in OA pathogenesis remained uninvestigated.

Purpose of the Study:

• To investigate the therapeutic potential of tangeretin against osteoarthritis.
• To elucidate the underlying molecular mechanisms of tangeretin's anti-osteoarthritis effects.

Main Methods:

• In vitro studies utilized cultured human articular chondrocytes stimulated with interleukin-1β (IL-1β) to assess tangeretin's effects on inflammatory mediators and ECM components.
• In vivo studies employed a destabilized medial meniscus (DMM) mouse model to evaluate tangeretin's efficacy in preventing cartilage degradation.
• Molecular analyses included quantitative polymerase chain reaction (qPCR), Western blot, ELISA, reactive oxygen species (ROS) detection, and various staining techniques.

Main Results:

• Tangeretin significantly inhibited IL-1β-induced secretion of inflammatory mediators and ECM degradation in chondrocytes.
• In vivo, tangeretin treatment abrogated DMM-induced cartilage damage in mice.
• Mechanistically, tangeretin suppressed OA progression by activating the Nrf2/HO-1 axis, inhibiting NF-κB activation, and modulating the MAPK signaling pathway.

Conclusions:

• Tangeretin demonstrates significant anti-osteoarthritis effects by mitigating inflammation and ECM degradation in both cellular and animal models.
• The therapeutic action of tangeretin is attributed to its modulation of the Nrf2/NF-κB and MAPK/NF-κB signaling pathways.
• Tangeretin emerges as a promising candidate for future osteoarthritis therapeutic strategies.