Evidence map›Paper›PMID 42308665›Full record

ArticleInternational dental journal2026

Melatonin Rescues Enamel Defects Induced by Maternal Circadian Disruption via Targeting the BMAL1-JNK3 Axis.

Xuanyu Wang, Jing Liu, Mengning Bi, Xue Li, Xuejiao Yang, Wenke Xu, Zhihua Chen, Yueying Wang, Fang Ji

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In one paragraph

Article in International dental journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Xuanyu WangDepartment of Orthodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University, School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Jing LiuDepartment of Orthodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University, School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Mengning BiDepartment of Orthodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University, School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Xue LiShanghai institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xuejiao YangShanghai institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wenke XuDepartment of Orthodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University, School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Zhihua ChenDepartment of Orthodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University, School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Yueying WangShanghai institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yywang@shsmu.edu.cn.
Fang JiDepartment of Orthodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University, School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China. Electronic address: smilefang98@sjtu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

INTRODUCTION AND

aimsDevelopmental defects of enamel (DDE) are highly prevalent, yet effective preventive measures remain elusive. The process of amelogenesis exhibits intrinsic circadian rhythmicity. While the photoperiod-regulated hormone melatonin is a recognized modulator of bone formation, its potential role in coordinating the circadian aspects of enamel biomineralization remains incompletely understood. This study aimed to decipher the impact of aberrant photoperiods on enamel development and to identify melatonin's regulatory targets.

methodsWe assessed the impact of maternal circadian disruption on offspring enamel mineralization using 3D X-ray microscopy (3DXRM), ATR-FTIR, SEM, Western blot, and qRT-PCR. Plasma melatonin concentration was measured by ELISA. Melatonin was administered to pregnant mice under circadian disruption to investigate its effects on enamel mineralization in their offspring. To investigate the molecular mechanisms downstream of BMAL1, we performed Bmal1 knockdown in ameloblast-lineage cells (ALCs) and used RNA sequencing and siRNA transfection.

resultsCircadian disruption impaired enamel mineralization (reduced thickness/density, increased CO₃²⁻/PO₄³⁻ ratio, rough surface with disorganized prisms), which was partially rescued by melatonin. Bmal1 knockdown in ALCs disrupted mitochondrial respiration, increased JNK3 phosphorylation, and reduced mineralization; melatonin restored mitochondrial function and suppressed JNK3 overactivation.

conclusionMechanistically, melatonin inhibits JNK3 phosphorylation to restore enamel mineralization. Bmal1 knockdown impairs the mitochondrial respiratory electron transport chain, while melatonin restores its function, thereby suppressing JNK3 overactivation and ultimately promoting mineralization. CLINICAL RELEVANCE: The BMAL1-JNK3 axis is a therapeutic target for enamel mineralization, providing a novel theoretical basis for perinatal circadian regulation.

Indexed as

ARNTL Transcription FactorsCircadian RhythmDental EnamelMelatoninAmeloblastsAmelogenesisAnimalsBlotting, WesternFemaleMiceMicroscopy, Electron, ScanningPregnancyARNTL Transcription FactorsBmal1 protein, mouseMelatoninAmelogenesisBMAL1Circadian rhythmJNK3Melatonin

Identifiers

PMID42308665
PMCPMC13284480

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.