2. Academic Validation
  3. EBV promotes alveolar trabecula resorption via extracellular vesicle remodeling by group IIA secreted phospholipase A2

EBV promotes alveolar trabecula resorption via extracellular vesicle remodeling by group IIA secreted phospholipase A2

  • J Lipid Res. 2026 Mar 3;67(4):101014. doi: 10.1016/j.jlr.2026.101014.
Akane Kanamori 1,  Akira Hasuike 2,  Kai Kudo 3,  Joaquim Carreras 4,  Takanobu Shimizu 3,  Shunya Nakayama 3,  Ryo Yanagiya 5,  Ryo Koike 6,  Yorimasa Ogata 7,  Osamu Takeichi 8,  Shuichi Sato 9,  Kiyoshi Ando 10,  Naoya Nakamura 4,  Makoto Murakami 11,  Kenichi Imai 12,  Ai Kotani 13
Affiliations

Affiliations

  • 1 Division of Cellular and Molecular Biology, Department of Regulation of Infectious Cancer, Research Institute for Microbial Diseases, The University of Osaka, Suita, Osaka, Japan; Department of Molecular Life Sciences, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
  • 2 Department of Innovative Medical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan; Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan.
  • 3 Department of Innovative Medical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
  • 4 Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
  • 5 Division of Cellular and Molecular Biology, Department of Regulation of Infectious Cancer, Research Institute for Microbial Diseases, The University of Osaka, Suita, Osaka, Japan.
  • 6 Department of Microbiology and Immunology, Nihon University School of Dentistry, Tokyo, Japan.
  • 7 Department of Periodontology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
  • 8 Department of Endodontics, Nihon University School of Dentistry, Tokyo, Japan.
  • 9 Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan.
  • 10 Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
  • 11 Laboratory of Microenvironmental Metabolic Health Sciences Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • 12 Department of Microbiology and Immunology, Nihon University School of Dentistry, Tokyo, Japan. Electronic address: [email protected].
  • 13 Division of Cellular and Molecular Biology, Department of Regulation of Infectious Cancer, Research Institute for Microbial Diseases, The University of Osaka, Suita, Osaka, Japan; Department of Immunology, Tokai University School of Medicine, Isehara, Kanagawa, Japan. Electronic address: [email protected].
PMID: 41786250 DOI: 10.1016/j.jlr.2026.101014
Abstract

Epstein-Barr virus (EBV) is an enveloped, double-stranded DNA virus that selectively infects primates. Periodontitis, a common inflammatory disease characterized by alveolar bone destruction, affects more than half of the global adult population. While EBV has been linked to periodontitis due to its pro-inflammatory effects and presence in the human periodontium, its effects on bone metabolism, particularly alveolar bone resorption, remain unclear. This study demonstrated that EBV Infection in humanized mice induced osteoclast differentiation and alveolar bone resorption, resulting in sparse trabecular bone patterns and increased lacunae resorption. Extracellular vesicles (EVs) from EBV-infected cells contained M-CSF, essential for osteoclast differentiation, and increased CTSK and RANKL expression in osteoclast precursor cells after uptake. EBV Infection increased the expression of group IIA-secreted Phospholipase A2 (sPLA2-IIA), which hydrolyzed EV membranes to produce lipid mediators such as lysophosphatidic acid (LPA) and arachidonic acid derivatives-both of which induce osteoclast differentiation. Treatment with the sPLA2 inhibitor varespladib reduced CTSK and RANKL expression in vitro and in vivo, confirming the role of sPLA2-IIA in osteoclastogenesis. Furthermore, sPLA2-IIA expression and metabolites were significantly elevated in EVs from the gingival crevicular fluid of EBV-positive patients with periodontitis. These findings suggest that sPLA2-IIA-mediated hydrolysis of EVs from EBV-infected cells contributes to alveolar bone loss, offering insights intotherapeutic strategies targeting EBV and sPLA2-IIA to prevent periodontitis progression.

Keywords

EBV; bone resorption; extracellular vesicles; periodontitis; sPLA(2).

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