2. Academic Validation
  3. Porphyromonas gingivalis extracellular vesicles exacerbated osteoporosis by disrupting osteoblast mitochondrial dynamics and inhibiting Cpt2-regulated fatty acid oxidation

Porphyromonas gingivalis extracellular vesicles exacerbated osteoporosis by disrupting osteoblast mitochondrial dynamics and inhibiting Cpt2-regulated fatty acid oxidation

  • J Nanobiotechnology. 2025 Oct 10;23(1):635. doi: 10.1186/s12951-025-03717-z.
Qiujing Qiu # 1,  Xiaoyuan Yan # 1,  Zeying Zhang 1,  Xiyue Zhang 1,  Jiawei Ma 1,  Wenqing Gao 1,  Na An 2,  Lihong Qiu 3,  Jiajie Guo 4
Affiliations

Affiliations

  • 1 Department of Endodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, 110001, China.
  • 2 Department of Orthodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, 110001, China. [email protected].
  • 3 Department of Endodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, 110001, China. [email protected].
  • 4 Department of Endodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, 110001, China. [email protected].
  • # Contributed equally.
PMID: 41074134 DOI: 10.1186/s12951-025-03717-z
Abstract

Background: Recent studies have implicated periodontitis (PD) as a potential risk factor for osteoporosis; however, the precise mechanisms remain unclear. Porphyromonas gingivalis (Pg), a key pathogen associated with PD, can secrete extracellular vesicles (EVs). However, whether Pg EVs can be transported to the bone marrow and influence osteoporosis-related osteoblast differentiation warrants exploration. This study compares Pg EVs with EVs from Porphyromonas endodontalis (Pe), which is a less virulent congener but the evidence for its pathogenicity in PD is weak.

Results: Pg EVs can be translocated into the marrow of mice and be internalized by osteoblasts through clathrin- and lipid raft-mediated endocytosis, thereby exacerbating osteoporosis. Pg EVs promote mitochondrial fission and inhibit mitochondrial fusion, leading to mitochondrial fragmentation, impaired mitochondrial activity and suppressed osteogenic differentiation. Furthermore, Pg EVs downregulate the protein level of carnitine palmitoyl transferase 2 (Cpt2) and inhibit fatty acid oxidation (FAO) by disrupting mitochondrial dynamics, which impairs osteoblast ATP production and exacerbates osteoporosis. The effects of Pe EVs are similar but weaker than those of Pg EVs.

Conclusions: This study elucidates that Pg EVs exacerbate osteoporosis by disrupting osteoblast mitochondrial dynamics and suppressing Cpt2-regulated FAO. This study contributes to understanding of the etiological mechanisms through which Pg contributes to the progression of osteoporosis and highlights the pivotal role of EVs in the association between periodontal disease and systemic diseases.

Keywords

Porphyromonas gingivalis; Carnitine palmitoyl transferase 2; Extracellular vesicles; Fatty acid oxidation; Mitochondrial dynamics; Osteoblast.

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