Fig. 9

Schematic diagram of the mechanism of ISO inhibition on RANKL-induced osteoclastogenesis. Our study demonstrated that ISO could inhibit osteoclastogenesis, potentially by inhibiting the activation of the MAPK and PI3K-AKT1 signaling pathways. Additionally, ISO could reduce intracellular ROS levels by promoting the expression and nuclear translocation of Nrf2 and increasing the level of antioxidant enzymes. Eventually, the downstream activation of key signaling cascades such as c-Fos and NFATc1 transcription factors was suppressed through the above mechanism of effect. ISO, Isoorientin; RANKL, receptor activator of nuclear factor‐κB ligand; RANK, receptor activator of nuclear factor-κB; Nrf2, Nuclear factor erythroid 2‐related factor 2; Keap1, Kelch-like ECH-associated protein 1; NFATc1, nuclear factor of activated T cells 1; c‐Fos, cellular oncogene Fos; ROS, reactive oxygen species; HO‐1, haem oxygenase‐1; CAT, catalase; GCLC, γ‐glutamyl cysteine synthetase catalytic subunit; TRAP, tartrate‐resistant acid phosphatase; CTSK, cathepsin K; MMP‐9, matrix metalloproteinase‐9