ArticleCells2020
DKK1 Induced by 1,25D3 Is Required for the Mineralization of Osteoblasts.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Pharmacodynamics of Oral Cholecalciferol in Healthy Individuals with Vitamin D Deficiency: A Randomized Open-Label Study.Nutrients · 2021Trial
- The effect of 1,25(OH)Clinical epigenetics · 2025Article
- TGF-β signaling regulates differentiation of MSCs in bone metabolism: disputes among viewpoints.Stem cell research & therapy · 2024Review
- MRL/MpJ Mice Resist to Age-Related and Long-Term Ovariectomy-Induced Bone Loss: Implications for Bone Regeneration and Repair.International journal of molecular sciences · 2023Article
- Review
- Dikkopf-1 promotes matrix mineralization of osteoblasts by regulating CaBMB reports · 2022Article
- Pleiotropic Effects of Vitamin D in Patients with Inflammatory Bowel Diseases.Journal of clinical medicine · 2022Review
- The functional roles of the circRNA/Wnt axis in cancer.Molecular cancer · 2022Review
- The Long, Dynamic Journey to the Elucidation of the Links Between Inflammation, Ectopic Bone Formation, and Wnt Signaling in Ankylosing Spondylitis.Journal of rheumatic diseases · 2022Article
- The TNF-NF-kB-DKK1 Axis Promoted Bone Formation in the Enthesis of Ankylosing Spondylitis.Journal of rheumatic diseases · 2021Article
- Blocking TNFα attenuates progressive cartilage matrix degradation in inflammatory arthritis.Experimental and therapeutic medicine · 2021Article
- 1ɑ,25-Dihydroxyvitamin DJournal of cellular and molecular medicine · 2021Article
- Vitamin K and D Supplementation and Bone Health in Chronic Kidney Disease-Apart or Together?Nutrients · 2021Review
- TGFβ1 Suppressed Matrix Mineralization of Osteoblasts Differentiation by Regulating SMURF1-C/EBPβ-DKK1 Axis.International journal of molecular sciences · 2020Article
- Effects of dihydrotestosterone on osteoblast activity in curdlan-administered SKG mice and osteoprogenitor cells in patients with ankylosing spondylitis.Arthritis research & therapy · 2020Article
- Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1α,25-dihydroxyvitamin D3 (1,25D3), the most popular drug for osteoporosis treatment, drives osteoblast differentiation and bone mineralization. Wnt/β-catenin signaling is involved in commitment and differentiation of osteoblasts, but the role of the Dickkopf-related protein 1 (DKK1), a Wnt antagonist, in osteoblasts remains unknown. Here, we demonstrate the molecular mechanism of DKK1 induction by 1,25D3 and its physiological role during osteoblast differentiation. 1,25D3 markedly promoted the expression of both CCAAT/enhancer binding protein beta (C/EBPβ) and DKK1 at day 7 during osteoblast differentiation. Interestingly, mRNA and protein levels of C/EBPβ and DKK1 in osteoblasts were elevated by 1,25D3. We also found that C/EBPβ, in response to 1,25D3, directly binds to the human DKK1 promoter. Knockdown of C/EBPβ downregulated the expression of DKK1 in osteoblasts, which was partially reversed by 1,25D3. In contrast, overexpression of C/EBPβ upregulated DKK1 expression in osteoblasts, which was enhanced by 1,25D3. Furthermore, 1,25D3 treatment in osteoblasts stimulated secretion of DKK1 protein within the endoplasmic reticulum to extracellular. Intriguingly, blocking DKK1 attenuated calcified nodule formation in mineralized osteoblasts, but not ALP activity or collagen synthesis. Taken together, these observations suggest that 1,25D3 promotes the mineralization of osteoblasts through activation of DKK1 followed by an increase of C/EBPβ.
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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 Socratic graph.