IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-56615-1.html
   My bibliography  Save this article

FTO-associated osteoclastogenesis promotes alveolar bone resorption in apical periodontitis male rat via the HK1/USP14/RANK pathway

Author

Listed:
  • Yajie Qian

    (Nanjing University)

  • Jing Wu

    (Medical School of Nanjing University)

  • Weidong Yang

    (Nanjing University)

  • Ruining Lyu

    (Medical School of Nanjing University)

  • Qiao You

    (Medical School of Nanjing University)

  • Jingjing Li

    (Nanjing University)

  • Qin He

    (Nanjing University)

  • Yuan Zhuang

    (Nanjing University)

  • Wenmei Wang

    (Nanjing University)

  • Yong Wang

    (Medical School of Nanjing University)

  • Yanan Zhu

    (Nanjing University)

  • Zhiwei Wu

    (College of Pharmacy, Dali University
    Center for Public Health Research, Medical School of Nanjing University)

  • Deyan Chen

    (Medical School of Nanjing University)

Abstract

Alveolar bone resorption (ABR) is a key pathological manifestation in the development of apical periodontitis (AP) and contributes to the AP-associated tooth loss among AP patients in the clinic. However, the underlying mechanism of ABR development is largely unknown. Here we show, the total levels of N6-methyladenosine (m6A) were reduced in AP male rat alveolar bone tissues and BMDM-derived osteoclasts (OC), which was associated with the up-regulation of obesity-associated protein (FTO). Subsequently FTO-mediated hexokinase (HK1) demethylation modification enhancing glycolytic pathway that stabilizes receptor activator of NF-κB (RANK) protein via the deubiquitination activity of ubiquitin-specific protease 14 (USP14), which further promotes osteoclastogenesis to participate in the AP-related ABR development. Finally, Dac51 (an FTO inhibitor) and 2-DG (an HK1 inhibitor) both exhibit the inhibitory activity of osteoclastogenesis. Our current study reveals a molecular mechanism on osteoclastogenesis-related ABR and provides a therapeutic target of AP via modulating the FTO/HK1/USP14/RANK axis.

Suggested Citation

  • Yajie Qian & Jing Wu & Weidong Yang & Ruining Lyu & Qiao You & Jingjing Li & Qin He & Yuan Zhuang & Wenmei Wang & Yong Wang & Yanan Zhu & Zhiwei Wu & Deyan Chen, 2025. "FTO-associated osteoclastogenesis promotes alveolar bone resorption in apical periodontitis male rat via the HK1/USP14/RANK pathway," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56615-1
    DOI: 10.1038/s41467-025-56615-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-56615-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-56615-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Tetsuya Yoshimoto & Mizuho Kittaka & Andrew Anh Phuong Doan & Rina Urata & Matthew Prideaux & Roxana E. Rojas & Clifford V. Harding & W. Henry Boom & Lynda F. Bonewald & Edward M. Greenfield & Yasuyos, 2022. "Osteocytes directly regulate osteolysis via MYD88 signaling in bacterial bone infection," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. William J. Boyle & W. Scott Simonet & David L. Lacey, 2003. "Osteoclast differentiation and activation," Nature, Nature, vol. 423(6937), pages 337-342, May.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Nidhi Rohatgi & Wei Zou & Yongjia Li & Kevin Cho & Patrick L. Collins & Eric Tycksen & Gaurav Pandey & Carl J. DeSelm & Gary J. Patti & Anwesha Dey & Steven L. Teitelbaum, 2023. "BAP1 promotes osteoclast function by metabolic reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Jiahui Du & Yili Liu & Jinrui Sun & Enhui Yao & Jingyi Xu & Xiaolin Wu & Ling Xu & Mingliang Zhou & Guangzheng Yang & Xinquan Jiang, 2024. "ARID1A safeguards the canalization of the cell fate decision during osteoclastogenesis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Wenquan Liang & Ru Feng & Xiaojia Li & Xingwei Duan & Shourui Feng & Jun Chen & Yicheng Li & Junqi Chen & Zezheng Liu & Xiaogang Wang & Guangfeng Ruan & Su’an Tang & Changhai Ding & Bin Huang & Zhipen, 2024. "A RANKL-UCHL1-sCD13 negative feedback loop limits osteoclastogenesis in subchondral bone to prevent osteoarthritis progression," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Lavinia Paternoster & Mattias Lorentzon & Liesbeth Vandenput & Magnus K Karlsson & Östen Ljunggren & Andreas Kindmark & Dan Mellstrom & John P Kemp & Caroline E Jarett & Jeff M P Holly & Adrian Sayers, 2010. "Genome-Wide Association Meta-Analysis of Cortical Bone Mineral Density Unravels Allelic Heterogeneity at the RANKL Locus and Potential Pleiotropic Effects on Bone," PLOS Genetics, Public Library of Science, vol. 6(11), pages 1-12, November.
    5. Jialiang S. Wang & Tushar Kamath & Courtney M. Mazur & Fatemeh Mirzamohammadi & Daniel Rotter & Hironori Hojo & Christian D. Castro & Nicha Tokavanich & Rushi Patel & Nicolas Govea & Tetsuya Enishi & , 2021. "Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    6. Yasuaki Uehara & Yusuke Tanaka & Shuyang Zhao & Nikolaos M. Nikolaidis & Lori B. Pitstick & Huixing Wu & Jane J. Yu & Erik Zhang & Yoshihiro Hasegawa & John G. Noel & Jason C. Gardner & Elizabeth J. K, 2023. "Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Xiaming Du & Chao Zhang & Xiangqi Zhang & Zhen Qi & Sulin Cheng & Shenglong Le, 2021. "The Impact of Nordic Walking on Bone Properties in Postmenopausal Women with Pre-Diabetes and Non-Alcohol Fatty Liver Disease," IJERPH, MDPI, vol. 18(14), pages 1-10, July.
    8. M. Gabriele Bixel & Kishor K. Sivaraj & Melanie Timmen & Vishal Mohanakrishnan & Anusha Aravamudhan & Susanne Adams & Bong-Ihn Koh & Hyun-Woo Jeong & Kai Kruse & Richard Stange & Ralf H. Adams, 2024. "Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    9. Zhenxi Li & Xinghai Yang & Ruifeng Fu & Zhipeng Wu & Shengzhao Xu & Jian Jiao & Ming Qian & Long Zhang & Chunbiao Wu & Tianying Xie & Jiqiang Yao & Zhixiang Wu & Wenjun Li & Guoli Ma & Yu You & Yihua , 2024. "Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Wenjing Jin & Xianfeng Lin & Haihua Pan & Chenchen Zhao & Pengcheng Qiu & Ruibo Zhao & Zihe Hu & Yanyan Zhou & Haiyan Wu & Xiao Chen & Hongwei Ouyang & Zhijian Xie & Ruikang Tang, 2021. "Engineered osteoclasts as living treatment materials for heterotopic ossification therapy," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56615-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.