Ferulic acid induces osteoblast differentiation via activation of p38 MAPK

In this study, ferulic acid, a bioactive metabolite derived from Lactobacillus fermentum, was evaluated for its effects on osteoblastic differentiation using in vitro assays and Western blot analysis. In U2OS and MG63 osteoblast-like cells, ferulic acid treatment increased Angiopoietin-1 expression and tight junction–related proteins. Furthermore, key osteogenic markers, including alkaline phosphatase, bone sialoprotein, DLX5, osteocalcin, Osterix, RUNX2, and type I collagen, were significantly upregulated. Consistent with these findings, mineralization assays showed enhanced alkaline phosphatase activity and intensified Alizarin Red S staining, indicating increased mineral deposition. Mechanistically, ferulic acid stimulated the phosphorylation of p38 MAPK, which promoted RUNX2–Osterix complex formation. The activation of p38 MAPK was also essential for enhancing cell migration and mineralization. Collectively, these results demonstrate that ferulic acid promotes osteoblastic differentiation via p38 MAPK signaling, suggesting its potential application as a therapeutic agent for bone regeneration.