Vitamin D receptor (VDR) agonists supporting human osteoblast (hOB) differentiation in the absence of bone resorption are attractive agents in a bone regenerative setting. One potential candidate fulfilling these roles is 24,25-dihydroxy vitamin D3 (24,25D). Over forty years ago it was reported that supraphysiological levels of 24,25D could stimulate intestinal calcium uptake and aid bone repair without causing bone calcium mobilisation. VDR agonists co-operate with certain growth factors to enhance hOB differentiation but whether 24,25D might act similarly in promoting cellular maturation has not been described. Given our discovery that lysophosphatidic acid (LPA) co-operated with VDR agonists to enhance hOB maturation, we co-treated MG63 hOBs with 24,25D and a phosphatase-resistant LPA analog. In isolation 24,25D inhibited proliferation and stimulated osteocalcin expression. When co-administered with the LPA analog there were synergistic increases in alkaline phosphatase (ALP). These are encouraging findings which may help realise the future application of 24,25D in promoting osseous repair.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.steroids.2014.01.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pembrolizumab ± paricalcitol in metastatic pancreatic cancer postmaximal cytoreduction.
Oncologist
January 2025
HonorHealth Research Institute, Scottsdale, AZ, United States.
Lessons Learned: Intravenous paricalcitol did not improve the efficacy of pembrolizumab, likely related to the short half-life.
Background: Immunotherapy has limited benefit in the treatment of advanced pancreatic cancer with the tumor microenvironment playing a key role in immune resistance. In preclinical studies, vitamin D receptor (VDR) agonists have been shown to sensitize pancreatic tumors to PD-1 blockade.
Design, synthesis, and anti-liver fibrosis activity of novel non-steroidal vitamin D receptor agonists based on open-ring steroid scaffold.
Eur J Med Chem
January 2025
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address:
Vitamin D receptor (VDR) has emerged as a crucial target for the treatment of hepatic fibrosis, a condition characterized by excessive deposition of extracellular matrix (ECM) components leading to impaired liver function. Activation of VDR has been shown to inhibit the transformation of hepatic stellate cells (HSCs), which play a key role in the development of liver fibrosis, thus reducing ECM production. In this study, a series of 37 non-steroidal VDR agonists with novel scaffold were designed and synthesized utilizing the scaffold hopping strategy.
View Article and Find Full Text PDFHypoxia Compromises the Differentiation of Human Osteosarcoma Cells to CAR-R, a Hydroxylated Derivative of Lithocholic Acid and Potent Agonist of the Vitamin D Receptor.
Int J Mol Sci
January 2025
School of Applied Sciences, College of Health, Science and Society, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK.
The active metabolite of vitamin D3, calcitriol (1,25D), is widely recognised for its direct anti-proliferative and pro-differentiation effects. However, 1,25D is calcaemic, which restricts its clinical use for cancer treatment. Non-calcaemic agonists of the vitamin D receptor (VDR) could be better candidates for cancer treatment.
View Article and Find Full Text PDFVitamin D receptor regulates methyltransferase like 14 to mitigate colitis-associated colorectal cancer.
J Genet Genomics
January 2025
Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. Electronic address:
Colitis-associated colorectal cancer (CAC), a serious complication of ulcerative colitis (UC), is associated with a poor prognosis. The vitamin D receptor (VDR) is recognized for its protective role in UC and CAC through the maintenance of intestinal barrier integrity and the regulation of inflammation. This study demonstrates a significant reduction in mA-related genes, particularly methyltransferase like 14 (METTL14), in UC and CAC patients and identifies an association between METTL14 and VDR.
View Article and Find Full Text PDFComparative Analyses of the Safety Profiles of Vitamin D Receptor Agonists: A Pharmacovigilance Study Based on the EudraVigilance Database.
Pharmaceuticals (Basel)
December 2024
Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania.
: Vitamin D receptor (VDR) agonists are commonly used in clinical practice for their roles in calcium regulation and potential benefits in various diseases. However, their safety profiles, particularly for compounds available as food supplements, remain underexplored in real-world settings. This study aimed to analyze the safety profiles of VDR agonists using the EudraVigilance database, focusing on adverse drug reactions (ADRs) reported between 1 January 2004 and 23 June 2024.
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!