ArticleFrontiers in cellular and infection microbiology2025
Gingipains disrupt bone homeostasis via dual regulation of osteogenesis and osteoclastogenesis through exosomal miR-146a-5p/TRAF6 signaling.
Article in Frontiers in cellular and infection microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Application of Temporally Controlled Release Systems in Periodontal Tissue Regeneration: From Material Design to Therapeutic Strategies.Pharmaceutics · 2026Review
- Therapeutic Potential of Exosomes in Bone Infection: Mechanisms of Action, Engineering Strategies, and Translational Applications.International journal of nanomedicine · 2026Review
- Immunocyte-derived extracellular vesicles in osteoimmunology: mechanisms, disease contexts, and translational prospects.Frontiers in immunology · 2025Review
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Authors and funding
8 authors.
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Abstract
Background: Gingipains are virulence factors released by Methods: Clinical samples of gingival crevicular fluid, subgingival plaque, and gingival tissues were collected from 15 patients with stage III-IV periodontitis and 15 healthy controls. The effects of gingipains on bone marrow mesenchymal stem cells (BMSCs) and RAW264.7 macrophages were assessed using cell proliferation assays, qPCR, western blot, microarray analysis, and dual-luciferase reporter assays. A rat periodontitis model was used to validate the findings Results: Periodontitis patients exhibited elevated levels of lysine- and arginine-specific gingipains, C5a, and RANKL (p < 0.05). Gingipains inhibited BMSCs proliferation and osteogenic differentiation in a dose-dependent manner while promoting osteoclastogenesis in RAW264.7 macrophages through BMSCs-derived exosomes. Gingipains reduced the levels of miR-146a-5p in exosomes, which enhanced osteoclast differentiation through the miR-146a-5p/TRAF6 signaling pathway. Animal models confirmed that gingipains aggravated alveolar bone loss, which was mitigated by miR-146a-5p overexpression. Conclusion: Gingipains disrupt bone metabolism by inhibiting BMSCs osteogenesis and promoting osteoclastogenesis through communication via exosomes. Targeting miR-146a-5p offers a potential therapeutic approach to counter gingipain-induced periodontal destruction.
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