Evidence map›Paper›PMID 42389279›Full record

ArticleFrontiers in pharmacology2026

Circadian rhythm disruption impairs time-dependent dentine regeneration and reprograms the late-stage dental proteome in a mouse pulp injury model.

Melike Guvendi, Hayriye E Yelkenci, Elif Ozbay, Halil I Koc, Olgu E Tok, Serdar Altunay, Ertugrul Kilic, Mustafa Gundogar, Mustafa C Beker

Abstract read
In one paragraph

Article in Frontiers in pharmacology, 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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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Melike GuvendiDepartment of Endodontics, Faculty of Dentistry, İstanbul Medipol University, İstanbul, Türkiye.
Hayriye E YelkenciRegenerative and Restorative Medical Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Türkiye.
Elif OzbayRegenerative and Restorative Medical Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Türkiye.
Halil I KocRegenerative and Restorative Medical Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Türkiye.
Olgu E TokRegenerative and Restorative Medical Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Türkiye.
Serdar AltunayRegenerative and Restorative Medical Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Türkiye.
Ertugrul KilicRegenerative and Restorative Medical Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Türkiye.
Mustafa GundogarDepartment of Endodontics, Faculty of Dentistry, İstanbul Medipol University, İstanbul, Türkiye.
Mustafa C BekerRegenerative and Restorative Medical Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Türkiye.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Circadian rhythms coordinate metabolic and regenerative programs, yet their contribution to pulp healing and tertiary dentinogenesis remains unclear. Here, we investigated whether chronic circadian rhythm disruption (CRD) alters time-dependent dentine repair and proteomic remodeling after dental pulp injury (DPI) in male BALB/c mice. Animals were maintained either under a stable 12:12 h light-dark cycle or under a chronic jet-lag model with a daily 2 h phase advance. DPI was induced in the maxillary first molars, followed by immediate direct pulp capping with mineral trioxide aggregate and sealing with glass ionomer cement. Histological and histomorphometric analyses were performed at days 7, 28, and 56 post-injury, while open-field and light/dark transition tests were conducted on day 56. Untargeted LC-MS/MS proteomics was additionally performed on day-56 dental tissues to define injury-, circadian-, and dual-regulated molecular signatures. CRD produced a behavioral phenotype characterized by reduced locomotor activity and increased anxiety-like behavior. Histology revealed a canonical reparative pattern after DPI, with peripheral tertiary dentine formation surrounding a central connective tissue core; however, CRD consistently attenuated newly formed dentine area at all time points, indicating compromised odontoblast-like differentiation and mineral deposition. Proteomic profiling identified extensive remodeling of the dental proteome, with injury- and CRD-dependent signatures converging on metabolic regulation, cytoskeletal dynamics, immune pathways, and extracellular matrix organization. Integrated analyses delineated 204 injury-specific proteins, 128 CRD-specific proteins, and 86 co-regulated proteins, resolving the response into injury-dominant, circadian-dominant, dual-regulated, and condition-independent modules. Collectively, these results demonstrate that chronic circadian misalignment impairs dentine regenerative capacity and reprograms the dental proteome, suggesting that circadian status may be an underappreciated determinant of outcomes in vital pulp therapy and regenerative endodontic procedures.

Indexed as

dental pulp injurydentine regenerationdentinogenesisproteomicsregenerative endodontic proceduresvital pulp therapy

Identifiers

PMID42389279
PMCPMC13321973

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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.