Progress of Wnt Signaling Pathway in Osteoporosis

Biomolecules. 2023 Mar 6;13(3):483. doi: 10.3390/biom13030483.

Abstract

Osteoporosis, one of the serious health diseases, involves bone mass loss, bone density diminishing, and degeneration of bone microstructure, which is accompanied by a tendency toward bone fragility and a predisposition to fracture. More than 200 million people worldwide suffer from osteoporosis, and the cost of treating osteoporotic fractures is expected to reach at least $25 billion by 2025. The generation and development of osteoporosis are regulated by genetic factors and regulatory factors such as TGF-β, BMP, and FGF through multiple pathways, including the Wnt signaling pathway, the Notch signaling pathway, and the MAPK signaling pathway. Among them, the Wnt signaling pathway is one of the most important pathways. It is not only involved in bone development and metabolism but also in the differentiation and proliferation of chondrocytes, mesenchymal stem cells, osteoclasts, and osteoblasts. Dkk-1 and SOST are Wnt inhibitory proteins that can inhibit the activation of the canonical Wnt signaling pathway and block the proliferation and differentiation of osteoblasts. Therefore, they may serve as potential targets for the treatment of osteoporosis. In this review, we analyzed the mechanisms of Wnt proteins, β-catenin, and signaling molecules in the process of signal transduction and summarized the relationship between the Wnt signaling pathway and bone-related cells. We hope to attract attention to the role of the Wnt signaling pathway in osteoporosis and offer new perspectives and approaches to making a diagnosis and giving treatment for osteoporosis.

Keywords: Dkk-1; SOST; Wnt signaling pathway; osteoblasts; osteoclasts; osteoporosis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Density
  • Bone and Bones / metabolism
  • Cell Differentiation
  • Humans
  • Osteoporosis* / genetics
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway* / genetics

Substances

  • Wnt Proteins

Grants and funding

The authors gratefully acknowledge the financial assistance provided by the Scientific Research Foundation of Tangshan Normal University (No. 2021A03), the Key Cultivation Project of Tangshan Normal University (No. ZDPY05), the Key Project for Scientific Research in Colleges and Universities of Hebei Province (No. ZD2021408), and the Natural Science Foundation of Hebei Province (No. 2021105001).