Probiotics demonstrate significant potential in activating osteoblasts through multiple molecular and clinical mechanisms. This study aimed to evaluate the potential of Lactobacillus fermentum for osteoblastic differentiation. L. fermentum significantly enhances osteoblastic differentiation and bone formation. In U2OS and MG63 osteoblast cells, live L. fermentum increased cell mobility, promoted wound healing, and raised angiopoietin1 expression. Key osteogenic proteins such as alkaline phosphatase, bone sialoprotein, DLX5, osteocalcin, Osterix, RUNX2, and type I collagen were upregulated following treatment. Mineralization assays confirmed higher alkaline phosphatase activity and Alizarin Red S staining, indicating enhanced mineral deposition. Mechanistically, L. fermentum strongly elevated p38 MAPK phosphorylation, which augments RUNX2 and Osterix interaction to regulate osteogenic gene transcription. These results demonstrate that L. fermentum may contribute to osteoblastic differentiation mainly via p38 MAPK pathway activation, supporting its potential as a resource for bone regeneration by stimulating osteogenic markers and mineralization processes.
Seong-Jin Park (Tue,) studied this question.