Ferulic Acid, a Dietary Polyphenol Suppresses Osteoclast Differentiation and Bone Erosion Via the Inhibition of RANKL Dependent NF-κB Signalling Pathway

Aims: Bone erosion induced by enhanced osteoclast formation is a debilitating pathological phenomenon in rheumatoid arthritis (RA). Recent finding has revealed that ferulic acid is associated with reduced osteoclast differentiation and bone erosion. However, the underlying mechanism through which ferulic acid inhibited osteoclast differentiation and bone erosion still remains to be elucidated. 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.