2. Academic Validation
  3. ATF5-mediated mitochondrial UPR inhibited RANKL in Porphyromonas gingivalis LPS-treated osteoblasts

ATF5-mediated mitochondrial UPR inhibited RANKL in Porphyromonas gingivalis LPS-treated osteoblasts

  • Arch Oral Biol. 2026 May:185:106556. doi: 10.1016/j.archoralbio.2026.106556.
Tianrui Yang 1,  Weiman Sun 2,  Lang Lei 3
Affiliations

Affiliations

  • 1 Shanghai Jiading District Central Hospital, Shanghai, China; Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
  • 2 Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
  • 3 Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China. Electronic address: [email protected].
PMID: 41759254 DOI: 10.1016/j.archoralbio.2026.106556
Abstract

Objective: The purpose of this study was to investigate whether mitochondrial unfolded protein response (UPRmt) was induced in Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS)-treated osteoblasts and to study the relationship among UPRmt, mitochondrial function and bone resorption in periodontitis.

Design: Osteoblasts were treated with P.gingivalis-LPS. Nicotinamide riboside (NR) and doxycycline (DOX) were used to enhance UPRmt, while small interference RNA was transfected to knock down activating transcription factor 5 (ATF5). Protein and mRNA levels of genes involved in UPRmt and bone metabolism were measured. Intracellular Reactive Oxygen Species (ROS), mitochondrial ROS and mitochondrial membrane potential were detected by flow cytometry and confocal imaging.

Results: UPRmt and receptor activator of NF-κB ligand (RANKL) expression were induced in P. gingivalis-LPS-treated osteoblasts. Enhancement of UPRmt by NR or DOX decreased RANKL and RANKL/Osteoprotegerin (OPG) ratio in osteoblasts. UPRmt inhibition by ATF5 knockdown aggravated mitochondrial dysfunction and promoted RANKL expression in P.gingivalis-LPS-treated osteoblasts.

Conclusions: ATF5-mediated UPRmt regulates RANKL expression through mtROS and mitochondrial membrane potential. UPRmt could be a potential target involved in the regulation of bone resorption in periodontitis.

Keywords

Activating transcription factor 5; Mitochondrial unfolded protein response; Porphyromonas gingivalis; Reactive oxygen species.

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