REVIEW article
Front. Pharmacol.
Sec. Predictive Toxicology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1669222
The Canonical Wnt Pathway in Osteoporosis: A Scoping Review of Key Compounds and Proteins Modulating Wnt-Induced Osteogenesis
Provisionally accepted
Nyruz Elahmer1
Sok Kuan Wong1Nur Khadijah Muhamad Jamil1Isa Naina Mohamed1
Sabarul Mokhtar2
Norliza Muhammad1*- 1Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia, Universiti Kebangsaan Malaysia, Bangi, Malaysia
- 2Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia, Universiti Kebangsaan Malaysia, Bangi, Malaysia
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The canonical Wnt pathway-a key regulator of bone formation and remodelinghas emerged as a promising target for osteoporosis therapy. This scoping review aims to map the key compounds and proteins modulating Wnt-induced osteogenesis, providing a comprehensive overview of the current literature and identifying research gaps.Methods: A systematic search was conducted in Ovid and PubMed for studies published between June 2017 and February 2024. Two independent reviewers screened titles, abstracts, and full texts. Data were extracted and synthesized narratively.Results: Among 91 articles identified, 15 met the inclusion criteria. External compounds such as LG-HMF, cerium oxide nanoparticles, 6% Sr-MSNs, and platelet-rich plasma (PRP) were found to stimulate Wnt signaling, promoting osteogenesis and inhibiting osteoclastogenesis via diverse mechanisms. Molecular agents including β-sitosterol and fluoxetine also modulated the pathway, suggesting novel therapeutic opportunities. Internal regulators such as LINC01119, QKI, and PITX1 inhibited Wnt activity and were associated with bone loss, while GNAS, GCN5, and Ca(v)1.2 activated the pathway, enhancing bone health. The review highlights intricate crosstalk between canonical and non-canonical Wnt pathways in bone remodeling. Clinical and epidemiological studies further confirmed the relevance of Wnt signaling by linking specific genetic and protein markers to bone mineral density and fracture risk.This scoping review highlights the dual role of Wnt pathway modulatorsstimulators enhance bone formation, while inhibitors contribute to osteoporosisemphasizing its potential in guiding targeted therapies and identifying genetic markers for personalized osteoporosis treatment.
Keywords: Wnt signaling, Osteogenesis, Bone formation, Scoping review, β-catenin, Bone health
Received: 19 Jul 2025; Accepted: 10 Sep 2025.
Copyright: © 2025 Elahmer, Wong, Jamil, Mohamed, Mokhtar and Muhammad. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Norliza Muhammad, azlina@ppukm.ukm.edu.my
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.