Ferulic acid, a dietary polyphenol suppresses osteoclast differentiation and bone erosion via the inhibition of RANKL dependent NF- κB signalling pathway

This study assessed the therapeutic effects of ferulic acid on osteoclast differentiation and bone erosion by targeting RANKL dependent NF-κB pathway. Main methods RAW 264.7 monocyte/macrophage cells were left untreated/treated with 25, 50 and 100 μM ferulic acid prior to stimulation with/without RANKL and M-CSF. Osteoclast differentiation and formation was assessed by SEM and TRAP analysis whereas its functional activity of bone erosion was determined by pit formation assay. Crucial transcription factors (NF-κBp-65, NFATc1 and c-Fos) and osteoclast specific genes (TRAP, MMP-9 and Cathepsin K) were evaluated by quantitative RT-PCR. Further, the protein level expression of NF-κBp-65, NFAtc1, c-Fos and MMP-9 was assessed using western blot analysis. Key findings Our results demonstrated that ferulic acid significantly attenuated RANKL induced osteoclast differentiation as evidenced from SEM and TRAP staining analysis. A remarkable decrease in the bone resorption activity of osteoclasts was also noticed upon ferulic acid treatment. In addition, the down-regulation of RANKL induced NF-κB activation and its associated downstream factors like NFATc1, c-Fos, TRAP, Cathepsin K and MMP-9 was also observed upon ferulic acid treatment. Significance Thus, our findings evidence the anti-stimulatory and anti-resorptive role of ferulic acid via the inhibition of RANKL dependent NF-κB signalling pathway. Graphical abstract
Source: Life Sciences - Category: Biology Source Type: research