| RRC ID |
86948
|
| Author |
Kanamori A, Hasuike A, Kudo K, Carreras J, Shimizu T, Nakayama S, Yanagiya R, Koike R, Ogata Y, Takeichi O, Sato S, Ando K, Nakamura N, Murakami M, Imai K, Kotani A.
|
| Title |
EBV Promotes Alveolar Trabecula Resorption via Extracellular Vesicle Remodeling by Group IIA Secreted Phospholipase A2.
|
| Journal |
J Lipid Res
|
| 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 over 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 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 gingival crevicular fluid of EBV-positive periodontitis patients. These findings suggest that sPLA2-IIA-mediated hydrolysis of EVs from EBV-infected cells contributes to alveolar bone loss, offering insights into therapeutic strategies targeting EBV and sPLA2-IIA to prevent periodontitis progression.
|
| Pages |
101014
|
| Published |
2026-3-3
|
| DOI |
10.1016/j.jlr.2026.101014
|
| PII |
S0022-2275(26)00040-4
|
| PMID |
41786250
|
| PMC |
PMC13049295
|
| MeSH |
Alveolar Bone Loss* / metabolism
Alveolar Bone Loss* / pathology
Alveolar Bone Loss* / virology
Animals
Cell Differentiation
Epstein-Barr Virus Infections* / metabolism
Epstein-Barr Virus Infections* / pathology
Epstein-Barr Virus Infections* / virology
Extracellular Vesicles* / metabolism
Group II Phospholipases A2* / metabolism
Herpesvirus 4, Human* / pathogenicity
Herpesvirus 4, Human* / physiology
Humans
Mice
Osteoclasts / metabolism
Osteoclasts / pathology
|
| IF |
4.483
|
| Resource |
| Cord blood stem cells for research |
RCB1189 |
