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LncRNA ZFAS1 Promotes Alveolar Bone Resorption by Enhancing Osteoclastogenesis in Periodontitis.

Lilliane Aol1, Xinhong Zhou1, Zheng Cao1

  • 1Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

Journal of Cellular Physiology
|January 19, 2026
PubMed
Summary

Long non-coding RNA ZFAS1 drives periodontitis-related bone loss by promoting osteoclast formation and inhibiting osteoblast activity. This study identifies ZFAS1 as a potential therapeutic target for inflammatory bone diseases.

Keywords:
alveolar bone resorptionlncRNA ZFAS1osteoblastogenesisosteoclastogenesisperiodontitis

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Area of Science:

  • Oral Biology
  • Molecular Biology
  • Genetics

Background:

  • Periodontitis causes persistent inflammation and destruction of tooth-supporting tissues.
  • The upstream regulators driving pathological bone loss in periodontitis remain unclear.
  • Long non-coding RNAs (lncRNAs) are emerging as key players in various biological processes, including bone remodeling.

Purpose of the Study:

  • To investigate the mechanistic role of lncRNA ZFAS1 in the dysregulated bone remodeling associated with periodontitis.
  • To explore ZFAS1's function in osteoclastogenesis and osteoblastogenesis in the context of periodontitis.

Main Methods:

  • Single-cell and bulk RNA sequencing of healthy and periodontitis-affected periodontal tissues.
  • Quantitative PCR (qPCR), histology, and immunohistochemistry for validation.
  • In vitro gain- and loss-of-function studies using RAW264.7 (osteoclast precursor) and MC3T3-E1 (osteoblast precursor) cell lines.

Main Results:

  • Periodontitis exhibits an 11-fold increase in the osteoclast-to-osteoblast ratio, with significant upregulation of lncRNA ZFAS1.
  • ZFAS1 expression positively correlates with early osteoclast marker genes (NFATC1, TRAP1) but not late-stage markers.
  • ZFAS1 overexpression promotes osteoclastogenesis and inhibits osteoblast differentiation and mineralization, while knockdown has opposite effects.

Conclusions:

  • lncRNA ZFAS1 is a critical driver of inflammatory bone loss in periodontitis.
  • ZFAS1 acts as a dual regulator, promoting osteoclastogenesis and inhibiting osteoblastogenesis.
  • ZFAS1 represents a potential therapeutic target for periodontitis and other bone loss conditions.