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  11. Betaine Alleviates Bisphosphonate-related Osteonecrosis Of The Jaw By Rescuing Bmscs Function In An M6a-mettl3-dependent Manner.
  1. Home
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  5. Biomedical And Clinical Sciences
  7. Dentistry
  9. Orthodontics And Dentofacial Orthopaedics
  11. Betaine Alleviates Bisphosphonate-related Osteonecrosis Of The Jaw By Rescuing Bmscs Function In An M6a-mettl3-dependent Manner.

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Betaine Alleviates Bisphosphonate-Related Osteonecrosis of the Jaw by Rescuing BMSCs Function in an m6A-METTL3-Dependent Manner.

Yizhou Jin1, Jiaxin Song1, Zhanqiu Diao1

  • 1Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing 100050, China.

International Journal of Molecular Sciences
|June 13, 2025

View abstract on PubMed

Summary
This summary is machine-generated.

Betaine supplementation can treat bisphosphonate-related osteonecrosis of the jaw (BRONJ). This study found betaine reversed impaired bone marrow stromal cell function and healed jaw lesions in a rat model, offering a new treatment insight.

Keywords:
N6-adenosine methylationbetainebisphosphonatemesenchymal stem cells

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Area of Science:

  • Biomedical Science
  • Epigenetics
  • Oral and Maxillofacial Surgery

Background:

  • Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of bisphosphonate (BP) therapy.
  • Current treatment strategies for BRONJ are limited, highlighting the need for novel therapeutic approaches.
  • Bisphosphonates impair orofacial bone marrow stromal cell (BMSC) function, potentially contributing to osteonecrosis development.

Purpose of the Study:

  • To investigate the role of N6-methyladenosine (m6A) modification in regulating BMSC function under BP stimulation.
  • To explore the therapeutic potential of betaine, a methyl donor, in treating BRONJ by targeting m6A modification.

Main Methods:

  • Examined m6A modification levels, SAM levels, and METTL3 expression in BMSCs exposed to BPs.
zoledronic acid
  • Assessed the effect of betaine on BP-induced BMSC dysfunction and osteogenic differentiation.
  • Utilized a BRONJ rat model to evaluate betaine's efficacy in vivo.

    • Main Results:

    • Bisphosphonates reduced global m6A methylation, SAM levels, and METTL3 expression in BMSCs during osteogenic differentiation.
    • Betaine administration reversed BP-induced decreases in m6A methylation and SAM levels, restoring BMSC differentiation capacity.
    • In a BRONJ rat model, betaine treatment attenuated bone lesions and accelerated wound healing.

    Conclusions:

    • m6A modification plays a crucial role in BMSC function under BP stimulation.
    • Betaine demonstrates therapeutic potential for BRONJ by restoring BMSC function and promoting bone healing.
    • Betaine offers a promising new therapeutic strategy for clinical management of BRONJ.