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Updated: Apr 15, 2026
Modeling Paracrine Noncanonical Wnt Signaling In Vitro
Published on: December 10, 2021
The WNT system: background and its role in bone
U H Lerner1,2, C Ohlsson1
1Centre for Bone and Arthritis Research, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Abstract:
WNTs are extracellular proteins that activate different cell surface receptors linked to canonical and noncanonical WNT signalling pathways. The Wnt genes were originally discovered as important for embryonic development of fruit flies and malignant transformation of mouse mammary cancers. More recently, WNTs have been implicated in a wide spectrum of biological phenomena and diseases. During the last decade, several lines of clinical and preclinical evidence have indicated that WNT signalling is critical for trabecular and cortical bone mass, and this pathway is currently an attractive target for drug development. Based on detailed knowledge of the different WNT signalling pathways, it appears that it might be possible to develop drugs that specifically target cortical and trabecular bone. Neutralization of a bone-specific WNT inhibitor is now being evaluated as a promising anabolic treatment for patients with osteoporosis. Here, we provide the historical background to the discoveries of WNTs, describe the different WNT signalling pathways and summarize the current understanding of how these proteins regulate bone mass by affecting bone formation and resorption.
Insights
WNT signalling pathways regulate bone mass. Targeting WNT inhibitors shows promise for osteoporosis treatment by promoting bone formation and resorption.
Area of Science:
- Molecular Biology
- Cell Biology
- Bone Biology
Background:
- WNTs are extracellular proteins crucial for embryonic development and cancer.
- WNT signalling pathways are increasingly recognized for their roles in diverse biological processes.
- Recent evidence highlights WNT signalling's critical role in maintaining trabecular and cortical bone mass.
Purpose of the Study:
- To provide a historical overview of WNT discoveries.
- To describe canonical and noncanonical WNT signalling pathways.
- To summarize WNTs' regulation of bone mass, focusing on bone formation and resorption.
Main Methods:
- Literature review of WNT signalling pathways.
- Analysis of preclinical and clinical evidence on WNTs and bone mass.
- Review of drug development targeting WNT pathways for bone disorders.
Main Results:
- WNT signalling pathways are essential for regulating both trabecular and cortical bone.
- WNTs influence bone mass by modulating bone formation and resorption processes.
- Targeting WNT signalling presents a promising therapeutic strategy for bone diseases.
Conclusions:
- Understanding WNT pathways offers opportunities for developing bone-specific drugs.
- Neutralizing bone-specific WNT inhibitors is a potential anabolic treatment for osteoporosis.
- WNT signalling is a key target for enhancing bone mass and treating bone loss.
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