Evidence mapPaperPMID 41636271Full record

ReviewJournal of periodontal research2026

The Role of Wnt Signaling in Age-Related Alveolar Bone Loss and Regeneration.

Hsiao H Sung, Navya Chalamalasetty, Ali Alzainal, Hanlong Liu, Lexuan Wang, Pietra Colacrai Arikita, Ivy C X Wei, Hom-Lay Wang, M H J van den Bosch, Michelle S Caird and 3 more

Abstract readReview
In one paragraph

Review in Journal of periodontal research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

1 citing paper in PubMed.

  1. Review
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

13 authors.

Hsiao H SungOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.ORCID https://orcid.org/0000-0001-6016-3838
Navya ChalamalasettyDepartment of Oral and Maxillofacial Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Ali AlzainalOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Hanlong LiuOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Lexuan WangOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Pietra Colacrai ArikitaOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Ivy C X WeiDepartment of Biologic and Materials Sciences & Prosthodontics, University of Michigan, Ann Arbor, Michigan, USA.
Hom-Lay WangDepartment of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, Michigan, USA.ORCID https://orcid.org/0000-0003-4238-1799
M H J van den BoschExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Centre, Nijmegen, the Netherlands.
Michelle S CairdOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Peter M van der KraanExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Centre, Nijmegen, the Netherlands.
Kenneth M KozloffOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.ORCID https://orcid.org/0000-0002-1108-7258
Esmeralda Blaney DavidsonExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Centre, Nijmegen, the Netherlands.ORCID https://orcid.org/0000-0003-3514-0313

Funding

Structure, Composition, & Histology Core - Core BP30AR069620 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$693k
NIAMS NIH HHS R21AR075197NIDCR NIH HHS 5K08DE030116NIDCR NIH HHS K08 DE030116NIH HHS P30AR069620
6 · The paper itself

Abstract

The periodontium is a uniquely dynamic tissue system requiring precise signaling for lifelong adaptation. The canonical Wnt/β-catenin pathway is a master regulator of bone homeostasis; however, its role in the specialized environment of the alveolar bone-marked by rapid turnover, complex mechanical forces, and exposure to the oral microbiome-remains incompletely understood, particularly in the context of aging. This review critically synthesizes evidence on Wnt signaling in alveolar bone remodeling, with a focus on age-related dysregulation, contrasting established paradigms from long bone biology with emerging oral-tissue-specific data. Wnt/β-catenin signaling is essential for periodontal homeostasis, orchestrating osteoblastogenesis and mechanotransduction. Its activity is compartment-specific within the periodontium and is potently suppressed in pathology. Key mechanisms of age-related decline include the upregulation of Wnt antagonists (e.g., sclerostin, DKK1), cellular senescence, altered FoxO-Wnt crosstalk under oxidative stress, and impaired mechanosensing. These changes converge to disrupt regenerative capacity, tipping the balance toward net alveolar bone loss. Therapeutically, sclerostin inhibition demonstrates robust preclinical efficacy in rescuing bone loss in models of periodontitis and estrogen deficiency. However, the potential cardiovascular risks of systemic Wnt activation suggest that redirecting efforts toward localized delivery strategies could be a promising alternative. Aging induces a multifaceted suppression of regenerative Wnt signaling in the periodontium. Modulating the Wnt pathway shows great potential for oral bone regeneration. However, significant challenges exist, especially in designing local delivery systems that are both safe and effective. Overcoming these hurdles is crucial for successful clinical applications. Future research must bridge the gap between skeletal biology and direct oral-specific investigations to enable targeted therapies that preserve periodontal health in an aging population.

Indexed as

AgingAlveolar Bone LossBone RegenerationWnt Signaling PathwayAnimalsBone RemodelingHumansMechanotransduction, Cellularagingalveolar boneperiodontiumWnt signaling

Identifiers

PMID41636271
PMCPMC13140785

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.