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REVIEW ARTICLE

The RANKL–OPG–RANK axis in orthodontic tooth movement: Crosstalk with Wnt/β-catenin and BMP signaling in osteoblast and osteoclast regulation

Feng Yan1 ,  Nor Dayana Binti Mohd Ali1*
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1 School of Dentistry, Lincoln University College, Petaling Jaya, Selangor Darul Ehsan, Malaysia
EJMO, 026150169 https://doi.org/10.36922/EJMO026150169
Received: 11 April 2026 | Revised: 1 June 2026 | Accepted: 9 June 2026 | Published online: 6 July 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Mechanically induced osteoclast-mediated bone resorption and osteoblast-mediated bone formation are the forces behind orthodontic tooth movement (OTM). Despite independent research on the RANKL/OPG/RANK axis, Wnt/β-catenin signaling, and BMP signaling, the crosstalk among these pathways in the context of OTM has not been systematically synthesized. The interplay of these pathways in the context of OTM would be crucial in the design of specific biological interventions to maximize the safety and efficacy of treatments. In this review, we mechanistically integrate evidence on the interaction among the RANKL/OPG/RANK axis, Wnt/β-catenin, and BMP signaling pathways to control osteoclastogenesis and osteoblastogenesis in human, animal, and in vitro OTM systems. We searched three databases (PubMed, Cochrane Library, LIVIVO) in April 2026. Following deduplication (n = 20) using Rayyan artificial intelligence, 58 records were screened through PRISMA in two phases. Inclusion criteria included OTM context, defined signaling pathway research with Wnt and/or BMP crosstalk, molecular/cellular outcome data, English language, and peer-reviewed primary research. Narrative synthesis was conducted across 21 studies. RANKL/OPG regulation was universally reported (21/21 studies). The upstream regulator was Wnt/β-catenin signaling (16/21), and the central mechanosensory-molecular mediator of force transduction and osteoclastogenesis in the presence of RANKL was sclerostin (11/21). BMP-2 was also identified as a mechanosensitive pro-osteogenic target (5/21). Compression-tension molecular asymmetry was also continuously observed, and the magnitude and duration of forces further influenced the dynamics of RANKL/OPG. The convergent mechanosensing pathways on the same RANKL/Wnt effector module were Piezo1, α7 nAChR, Ca2+ oscillations, and sympathetic β-AR. The RANKL/OPG/RANK axis and Wnt/β-catenin signaling constitute a highly connected regulatory system that regulates OTM bone remodeling. Sclerostin plays a central mechanosensory role in the translation of force to RANKL-mediated osteoclastogenesis. These results offer a molecular rationale to optimize OTM protocols and design specific therapeutics, especially in patients with impaired bone biology.

Keywords
Orthodontic tooth movement
Receptor activator of nuclear factor kappa-B ligand
Osteoprotegerin
Wnt/β-catenin
Sclerostin
Bone morphogenetic protein-2
Mechanotransduction
Signaling crosstalk
Funding
None.
Conflict of interest
The authors declare no conflicts of interest relevant to this work.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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