NDLI: Vitamin D Binding Protein and Monocyte Response to 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D: Analysis by Mathematical Modeling

Content Provider	PubMed Central
Author	Chun, Rene F. Peercy, Bradford E. Adams, John S. Hewison, Martin
Editor	Campbell, Moray
Copyright Year	2012
Abstract	Vitamin D binding protein (DBP) plays a key role in the bioavailability of active 1,25-dihydroxyvitamin D (1,25(OH)2D) and its precursor 25-hydroxyvitamin D (25OHD), but accurate analysis of DBP-bound and free 25OHD and 1,25(OH)2D is difficult. To address this, two new mathematical models were developed to estimate: 1) serum levels of free 25OHD/1,25(OH)2D based on DBP concentration and genotype; 2) the impact of DBP on the biological activity of 25OHD/1,25(OH)2D in vivo. The initial extracellular steady state (eSS) model predicted that 50 nM 25OHD and 100 pM 1,25(OH)2D), <0.1% 25OHD and <1.5% 1,25(OH)2D are ‘free’ in vivo. However, for any given concentration of total 25OHD, levels of free 25OHD are higher for low affinity versus high affinity forms of DBP. The eSS model was then combined with an intracellular (iSS) model that incorporated conversion of 25OHD to 1,25(OH)2D via the enzyme CYP27B1, as well as binding of 1,25(OH)2D to the vitamin D receptor (VDR). The iSS model was optimized to 25OHD/1,25(OH)2D-mediated in vitro dose-responsive induction of the vitamin D target gene cathelicidin (CAMP) in human monocytes. The iSS model was then used to predict vitamin D activity in vivo (100% serum). The predicted induction of CAMP in vivo was minimal at basal settings but increased with enhanced expression of VDR (5-fold) and CYP27B1 (10-fold). Consistent with the eSS model, the iSS model predicted stronger responses to 25OHD for low affinity forms of DBP. Finally, the iSS model was used to compare the efficiency of endogenously synthesized versus exogenously added 1,25(OH)2D. Data strongly support the endogenous model as the most viable mode for CAMP induction by vitamin D in vivo. These novel mathematical models underline the importance of DBP as a determinant of vitamin D ‘status’ in vivo, with future implications for clinical studies of vitamin D status and supplementation.
Related Links	http://dx.doi.org/10.1371/journal.pone.0030773
Starting Page	30773
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	1
Volume Number	7
Language	English
Publisher	Public Library of Science
Publisher Date	2012-01-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Editorial: Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions

Both 25-Hydroxyvitamin-D3 and 1,25-Dihydroxyvitamin-D3 Reduces Inflammatory Response in Human Periodontal Ligament Cells

Vitamin D-Binding Protein Directs Monocyte Responses to 25-Hydroxy- and 1,25-Dihydroxyvitamin D

25-Hydroxyvitamin D3 and 1,25-Dihydroxyvitamin D3 Promote the Differentiation of Human Subcutaneous Preadipocytes

Vitamin D Status and Pregnancy Complications: Serum 1,25-di-hydroxyl-Vitamin D and its Ratio to 25-hydroxy-Vitamin D are Superior Biomarkers than 25-hydroxy-Vitamin D

Independent Association of Low Serum 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels With All-Cause and Cardiovascular Mortality

In Pursuit of Vitamin D in Plants

Vitamin D in Fibromyalgia: A Causative or Confounding Biological Interplay?

The Risk of Acute Rejection Following Kidney Transplant by 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Status: A Prospective Cohort Study

Vitamin D Binding Protein and Monocyte Response to 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D: Analysis by Mathematical Modeling

Similar Documents

Editorial: Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions

Both 25-Hydroxyvitamin-D3 and 1,25-Dihydroxyvitamin-D3 Reduces Inflammatory Response in Human Periodontal Ligament Cells

Vitamin D-Binding Protein Directs Monocyte Responses to 25-Hydroxy- and 1,25-Dihydroxyvitamin D

25-Hydroxyvitamin D3 and 1,25-Dihydroxyvitamin D3 Promote the Differentiation of Human Subcutaneous Preadipocytes

Vitamin D Status and Pregnancy Complications: Serum 1,25-di-hydroxyl-Vitamin D and its Ratio to 25-hydroxy-Vitamin D are Superior Biomarkers than 25-hydroxy-Vitamin D

Independent Association of Low Serum 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels With All-Cause and Cardiovascular Mortality

In Pursuit of Vitamin D in Plants

Vitamin D in Fibromyalgia: A Causative or Confounding Biological Interplay?

The Risk of Acute Rejection Following Kidney Transplant by 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Status: A Prospective Cohort Study

Vitamin D Binding Protein and Monocyte Response to 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D: Analysis by Mathematical Modeling