1. Academic Validation
  2. Bacteria-mediated resistance of neutrophil extracellular traps to enzymatic degradation drives the formation of dental calculi

Bacteria-mediated resistance of neutrophil extracellular traps to enzymatic degradation drives the formation of dental calculi

  • Nat Biomed Eng. 2024 Mar 15. doi: 10.1038/s41551-024-01186-7.
Mei-Chen Wan # 1 Kai Jiao # 2 Yi-Na Zhu # 1 Qian-Qian Wan # 1 Yi-Peng Zhang 1 Long-Zhang Niu 1 Chen Lei 1 Jing-Han Song 1 Wei-Cheng Lu 1 Hua-Jie Liu 1 Zhao-Yang Ren 1 Franklin Tay 3 Li-Na Niu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
  • 2 Department of Stomatology, Tangdu hospital; State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
  • 3 The Dental College of Georgia, Augusta University, Augusta, GA, USA.
  • 4 State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China. niulina831013@126.com.
  • # Contributed equally.
Abstract

Dental calculi can cause gingival bleeding and periodontitis, yet the mechanism underlying the formation of such mineral build-ups, and in particular the role of the local microenvironment, are unclear. Here we show that the formation of dental calculi involves bacteria in local mature biofilms converting the DNA in neutrophil extracellular traps (NETs) from being degradable by the Enzyme DNase I to being degradation resistant, promoting the nucleation and growth of apatite. DNase I inhibited NET-induced mineralization in vitro and ex vivo, yet plasma DNases were ineffective at inhibiting ectopic mineralization in the oral cavity in rodents. The topical application of the DNA-intercalating agent chloroquine in rodents fed with a dental calculogenic diet reverted NET DNA to its degradable form, inhibiting the formation of calculi. Our findings may motivate therapeutic strategies for the reduction of the prevalence of the deposition of bacteria-driven calculi in the oral cavity.

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