Lactobacillus rhamnosus inhibits osteoclast differentiation by suppressing the TLR2/NF-κB pathway

Oral Dis. 2024 May;30(4):2373-2386. doi: 10.1111/odi.14712. Epub 2023 Aug 21.

Abstract

Objective: This study aimed to investigate the role of ultrasonicated Lactobacillus rhamnosus extract in osteoclast differentiation and its underlying mechanism, providing new strategies for the treatment of periodontitis.

Materials and methods: Osteoclasts were induced using macrophage colony-stimulating factor and receptor activator for nuclear factor-κB ligand. Lactobacillus rhamnosus extracts were obtained via ultrasonic crushing and ultracentrifugation. The effects of the LGG extract on osteoclast differentiation were evaluated, and the related signaling pathways were examined using western blotting. A mouse periodontitis model was established, and Lactobacillus rhamnosus extract was injected into the gingival sulcus to evaluate the inhibitory effect of Lactobacillus rhamnosus extract on alveolar bone resorption.

Results: At 50 μg/mL, Lactobacillus rhamnosus extract inhibited osteoclast differentiation with no effect on apoptosis and proliferation. This phenomenon was achieved by deactivating the NF-κB/c-Fos/NFATc1 signaling pathway through toll-like receptor 2. The in vivo results showed that the local injection of Lactobacillus rhamnosus extract suppressed osteoclast differentiation and alveolar bone resorption.

Conclusion: The ultrasonicated extract of Lactobacillus rhamnosus inhibited osteoclast differentiation by suppressing the activation of the NF-κB/c-Fos/NFATc1 pathway. Furthermore, it inhibited the destruction of the alveolar bone, providing a new strategy for the use of probiotics in the treatment of periodontitis.

Keywords: Lactobacillus rhamnosus; NF‐κB; osteoclast; periodontitis; toll‐like receptor 2.

MeSH terms

  • Alveolar Bone Loss / microbiology
  • Alveolar Bone Loss / therapy
  • Animals
  • Cell Differentiation* / drug effects
  • Disease Models, Animal
  • Lacticaseibacillus rhamnosus*
  • Male
  • Mice
  • NF-kappa B* / metabolism
  • NFATC Transcription Factors / metabolism
  • Osteoclasts* / drug effects
  • Periodontitis* / microbiology
  • Periodontitis* / therapy
  • Probiotics / pharmacology
  • Proto-Oncogene Proteins c-fos / metabolism
  • Signal Transduction*
  • Toll-Like Receptor 2*

Substances

  • Toll-Like Receptor 2
  • NF-kappa B
  • Tlr2 protein, mouse
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Proto-Oncogene Proteins c-fos