Wnt signaling in bone formation and its therapeutic potential for bone diseases
- 21 February 2013
- journal article
- Published by SAGE Publications in Therapeutic Advances in Musculoskeletal Disease
- Vol. 5 (1), 13-31
- https://doi.org/10.1177/1759720x12466608
Abstract
The Wnt signaling pathway plays an important role not only in embryonic development but also in the maintenance and differentiation of the stem cells in adulthood. In particular, Wnt signaling has been shown as an important regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. Induction of the Wnt signaling pathway promotes bone formation while inactivation of the pathway leads to osteopenic states. Our current understanding of Wnt signaling in osteogenesis elucidates the molecular mechanisms of classic osteogenic pathologies. Activating and inactivating aberrations of the canonical Wnt signaling pathway in osteogenesis results in sclerosteosis and osteoporosis respectively. Recent studies have sought to target the Wnt signaling pathway to treat osteogenic disorders. Potential therapeutic approaches attempt to stimulate the Wnt signaling pathway by upregulating the intracellular mediators of the Wnt signaling cascade and inhibiting the endogenous antagonists of the pathway. Antibodies against endogenous antagonists, such as sclerostin and dickkopf-1, have demonstrated promising results in promoting bone formation and fracture healing. Lithium, an inhibitor of glycogen synthase kinase 3β, has also been reported to stimulate osteogenesis by stabilizing β catenin. Although manipulating the Wnt signaling pathway has abundant therapeutic potential, it requires cautious approach due to risks of tumorigenesis. The present review discusses the role of the Wnt signaling pathway in osteogenesis and examines its targeted therapeutic potential.Keywords
This publication has 136 references indexed in Scilit:
- Wnt/β-Catenin Signaling and DiseaseCell, 2012
- Wnt6, Wnt10a and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis through a β-catenin-dependent mechanismBone, 2012
- Update on Wnt signaling in bone cell biology and bone diseaseGene, 2012
- Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiationJournal of Cellular Biochemistry, 2011
- Wnt10b deficiency results in age-dependent loss of bone mass and progressive reduction of mesenchymal progenitor cellsJournal of Bone and Mineral Research, 2010
- Modulation of Wnt signaling influences fracture repairJournal of Orthopaedic Research, 2010
- BMP‐2 modulates β‐catenin signaling through stimulation of Lrp5 expression and inhibition of β‐TrCP expression in osteoblastsJournal of Cellular Biochemistry, 2009
- Wnt/β-Catenin Signaling: Components, Mechanisms, and DiseasesDevelopmental Cell, 2009
- Secreted frizzled related protein 1 is a target to improve fracture healingJournal of Cellular Physiology, 2009
- Bone mass is inversely proportional to Dkk1 levels in miceBone, 2007