Lactobacillus gasseri-derived postbiotics promote osteogenic differentiation in BMSCs via ameliorating mitochondrial...

Craniomaxillofacial inflammatory bone defects, such as those in periodontitis, present significant regeneration challenges due to complex inflammatory microenvironments. Increasing attention has been directed toward the potential of probiotics and postbiotics in promoting osteogenesis and modulating inflammatory responses. This study aimed to elucidate the antioxidant and osteogenic effects of postbiotics from Lactobacillus gasseri ATCC 33323 on bone marrow mesenchymal stem cells (BMSCs).

The effects of postbiotics on BMSCs viability were assessed via MTT assay. Osteogenic differentiation was evaluated using RT-qPCR, ALP staining, Alizarin Red staining, and immunofluorescence. Antioxidant effects were examined by measuring ROS levels in H₂O₂-induced BMSCs. For in vivo analysis, postbiotics were incorporated into gelatin methacrylate (GelMA) and injected into rat calvarial defects, with bone regeneration assessed via micro-CT and histology analysis.

Postbiotics (150 μg/mL) significantly enhanced BMSC proliferation, migration, and osteogenic differentiation. They increased mRNA expression of ALP, OPN, OSTERIX, and Col-1, elevated RUNX2 and OPN protein levels, and stimulated ALP activity and calcium salt deposition. Additionally, postbiotics markedly reduced intracellular ROS in H₂O₂-induced BMSCs. In vivo, postbiotic treatment significantly enhanced bone regeneration and reduced local inflammation in calvarial defects.

Postbiotics from Lactobacillus gasseri promote BMSC osteogenic differentiation by alleviating mitochondrial oxidative stress, demonstrating potential as a therapeutic strategy for bone regeneration under inflammatory conditions.