ArticlePloS one2013
Crosstalk between Wnt/β-catenin and estrogen receptor signaling synergistically promotes osteogenic differentiation of mesenchymal progenitor cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 113 citations in OpenAlex.
- Foxq1-Wnt5a Axis Activation in Dental Papilla Stem Cells Promotes Odontogenesis on Acellular Matrix: A Laboratory Investigation.International endodontic journal · 2026Article
- The Role of Wnt Signaling in Age-Related Alveolar Bone Loss and Regeneration.Journal of periodontal research · 2026Review
- Ubiquitin-proteasome system regulation of bone remodeling in postmenopausal osteoporosis.Frontiers in cell and developmental biology · 2026Review
- β2-Adrenergic receptor regulates osteoblast differentiation and migration and C-terminal β-catenin phosphorylation.Biochemical and biophysical research communications · 2025Article
- An Update on Role of Ionizing Radiation to Enhance Proliferation and Differentiation of Normal Stem Cells via Activation of NRF2 Pathway: Review.Antioxidants (Basel, Switzerland) · 2025Review
- Effect of romosozumab on bone mineral density and trabecular bone score in premenopausal women with low bone mass.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Article
- Exploring estrogen-related mechanisms in ovarian carcinogenesis: association between bone mineral density and ovarian cancer risk in a multivariable Mendelian randomization study.Cancer causes & control : CCC · 2025Article
- Effective Bone Tissue Fabrication Using 3D-Printed Citrate-Based Nanocomposite Scaffolds Laden with BMP9-Stimulated Human Urine Stem Cells.ACS applied materials & interfaces · 2025Article
- The role of Wnt signalling in osteoporosis: A bibliometric analysis.Biomaterials translational · 2025Article
- Review
- Beyond the Gut: The intratumoral microbiome's influence on tumorigenesis and treatment response.Cancer communications (London, England) · 2024Review
- Exploring the effects of naringin on oxidative stress-impaired osteogenic differentiation via the Wnt/β-catenin and PI3K/Akt pathways.Scientific reports · 2024Article
- Review
- 17β-Estradiol (E2) Activates Matrix Mineralization through Genomic/Nongenomic Pathways in MC3T3-E1 Cells.International journal of molecular sciences · 2024Article
- A mixture ofHeliyon · 2024Article
- Effect of antibiotic monensin on cell proliferation and IGF1R signaling pathway in human colorectal cancer cells.Annals of medicine · 2023Article
- Altered Osteogenic Differentiation in Mesenchymal Stem Cells Isolated from Compact Bone of Chicken Treated with Varying Doses of Lipopolysaccharides.Biomolecules · 2023Article
- Wnt signaling: Essential roles in osteoblast differentiation, bone metabolism and therapeutic implications for bone and skeletal disorders.Genes & diseases · 2023Review
- A Review on Pathophysiology, and Molecular Mechanisms of Bacterial Chondronecrosis and Osteomyelitis in Commercial Broilers.Biomolecules · 2023Review
- Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteogenic differentiation from mesenchymal progenitor cells (MPCs) are initiated and regulated by a cascade of signaling events. Either Wnt/β-catenin or estrogen signaling pathway has been shown to play an important role in regulating skeletal development and maintaining adult tissue homeostasis. Here, we investigate the potential crosstalk and synergy of these two signaling pathways in regulating osteogenic differentiation of MPCs. We find that the activation of estrogen receptor (ER) signaling by estradiol (E2) or exogenously expressed ERα in MPCs synergistically enhances Wnt3A-induced early and late osteogenic markers, as well as matrix mineralization. The E2 or ERα-mediated synergy can be effectively blocked by ERα antagonist tamoxifen. E2 stimulation can enhance endochondral ossification of Wnt3A-transduced mouse fetal limb explants. Furthermore, exogenously expressed ERα significantly enhances the maturity and mineralization of Wnt3A-induced subcutaneous and intramuscular ectopic bone formation. Mechanistically, we demonstrate that E2 does not exert any detectable effect on β-catenin/Tcf reporter activity. However, ERα expression is up-regulated within the first 48h in AdWnt3A-transduced MPCs, whereas ERβ expression is significantly inhibited within 24h. Moreover, the key enzyme for the biosynthesis of estrogens aromatase is modulated by Wnt3A in a biphasic manner, up-regulated at 24h but reduced after 48h. Our results demonstrate that, while ER signaling acts synergistically with Wnt3A in promoting osteogenic differentiation, Wnt3A may crosstalk with ER signaling by up-regulating ERα expression and down-regulating ERβ expression in MPCs. Thus, the signaling crosstalk and synergy between these two pathways should be further explored as a potential therapeutic approach to combating bone and skeletal disorders, such as fracture healing and osteoporosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.