1alpha,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), the biologically active metabolite of vitamin D, mediates its actions via the vitamin D receptor (VDR), a member of the superfamily of steroid/thyroid hormone/retinoid receptors. 1,25-(OH)2D3 is required for calcium and phosphorus homeostasis, and for normal skeletal development as well as maintenance of skeletal architecture. Two VDR ligands, calcitriol (1,25-(OH)2D3) and its synthetic analog alfacalcidol (1alpha-hydroxyvitamin D3), have been approved for the treatment of osteoporosis. However, the use of calcitriol and alfacalcidol is limited by their major side effect, hypercalcemia, which is mediated mainly by VDR activity in the small intestine. In order to identify VDR ligands with less hypercalcemia liability, a number of pharmaceutical companies are pursuing efforts to develop synthetic vitamin D analogs. This review discusses the mechanism of action of vitamin D, and summarizes the currently approved anti-osteoporotic VDR agonists and compounds that are under development. The future directions of vitamin D research for the discovery of novel VDR agonists for osteoporosis are also discussed.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Association between serum 25-hydroxyvitamin D concentrations and urinary vitamin D metabolite concentrations measured by the NLucVDR assay.
J Steroid Biochem Mol Biol
January 2025
Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan. Electronic address:
It is well known that vitamin D is essential for human health; however, many people suffer from vitamin D deficiency or insufficiency worldwide, including in Japan. Serum 25-hydroxyvitamin D (25(OH)D) concentrations are typically measured to evaluate vitamin D status. In a previous study, we demonstrated that the concentrations of vitamin D metabolites in urine, measured using the NLucVDR assay system composed of a split-type nanoluciferase and the ligand-binding domain (LBD) of the human vitamin D receptor, correlated with serum 25(OH)D concentrations measured using liquid chromatography-mass spectrometry (LC-MS) or electrochemiluminescence immunoassays (ECLIAs).
View Article and Find Full Text PDFA comparative study on the antioxidant and antiglycation properties of different vitamin D forms.
Eur J Med Chem
January 2025
Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, 2c Mickiewicza Street, 15-233, Bialystok, Poland. Electronic address:
Vitamin D plays multiple roles in the body. Recently, there has been an increase in its popularity and growing interest in vitamin D supplementation. However, the mechanisms of vitamin D action have not yet been sufficiently explored.
View Article and Find Full Text PDFis overexpressed in keloid keratinocytes and its inhibition alters profibrotic gene expression.
Burns Trauma
January 2025
Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA.
Background: Keloids are disfiguring, fibrotic scar-like lesions that are challenging to treat and commonly recur after therapy. A deeper understanding of the mechanisms driving keloid formation is necessary for the development of more effective therapies. Reduced vitamin D receptor (VDR) expression has been observed in keloids, implicating vitamin D signaling in keloid pathology.
View Article and Find Full Text PDFVitamin D-VDR and vitamin A-RAR affect IL-13 and IFNγ secretion from human CD4 T cells directly and indirectly via competition for their shared co-receptor RXR.
Scand J Immunol
January 2025
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
The effects of vitamin D and vitamin A in immune cells are mediated through the vitamin D receptor (VDR) and retinoic acid receptor (RAR), respectively. These receptors share the retinoid X receptor (RXR) co-factor for transcriptional regulation. We investigated the effects of active vitamin D (1,25(OH)D) and 9-cis retinoic acid (9cRA) on T helper (T)1 and T2 cytokines and transcription factors in primary human blood-derived CD4 T cells.
View Article and Find Full Text PDFIntegrating network pharmacology with molecular docking and dynamics to uncover therapeutic targets and signaling mechanisms of vitamin D3 in Parkinson's disease.
Mol Divers
January 2025
School of Medicine, Zhejiang University, Hangzhou, 310000, Zhejiang, People's Republic of China.
Parkinson's disease (PD) is a chronic neurodegenerative disorder marked by dopaminergic neuron degeneration in the substantia nigra. Emerging evidence suggests vitamin D3 (VD) plays a therapeutic role in PD, but its precise molecular mechanisms remain unclear. This study employed network pharmacology and bioinformatics to identify VD's hub targets and related pathways.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!