The final, formatted version of the article will be published soon.
BRIEF RESEARCH REPORT article
Front. Dent. Med
Sec. Periodontics
Volume 5 - 2024 |
doi: 10.3389/fdmed.2024.1449482
Single nucleotide polymorphism rs854560 in paraoxonase-1 regulates the cytodifferentiation of human periodontal ligament cells
Provisionally accepted- Osaka University, Suita, Ōsaka, Japan
Aggressive periodontitis (AgP), classified as Stages III or IV and grade C periodontitis, is characterized by the rapid destruction of periodontal tissue. Genetic factors contribute to the pathogenesis of this disease, and familial aggregation of periodontitis is often observed. However, the mechanisms underlying the onset or progression of AgP have not been elucidated. Previously, we performed exome sequencing and identified AgP risk factors in Japanese AgP-patients. However, the small sample size limited our scope for detecting some of the true AgP genetic risk factors. To overcome this limitation, we searched for AgP-related genes more comprehensively from the whole exome sequencing data of the Japanese AgPpatients by extending the filtering criteria range. We identified seven AgP-associated suggestive genes, including the single nucleotide polymorphism (SNP) rs854560 in paraoxonase-1 (PON-1), which is correlated with AgP. However, the mechanism(s) underlying the induction of AgP pathogenesis by the SNP rs854560 PON-1 has not been elucidated. Thus, we further analyzed the functions of the SNP rs854560 PON-1 in human periodontal ligament (HPDL) cells through transfection of the wild-type PON-1 (WT) or SNP rs854560 PON-1 (mut) into HPDL cells. Real-time PCR indicated that mut had higher mRNA expression of osteogenic related-genes and showed a higher tendency of ALP activity and proliferation. The result suggested that WT PON-1 contributes to periodontal tissue homeostasis through appropriate proliferation and cytodifferentiation of HPDL cells, while SNP rs854560 PON-1 may mediate excessive calcification of periodontal tissue due to hyper proliferation of HPDL cells, thereby increasing the risk of AgP.
Keywords: exome sequencing, Single nucleotide polymorphism, Aggressive Periodontitis, Paraoxonase-1, Periodontal ligament cells
Received: 15 Jun 2024; Accepted: 26 Aug 2024.
Copyright: © 2024 Risa, Fujihara, Matsumoto, Kitagaki and Murakami. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chiharu Fujihara, Osaka University, Suita, 565-0871, Ōsaka, Japan
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.