scholarly journals No Role of Osteocytic Osteolysis in the Development and Recovery of the Bone Phenotype Induced by Severe Secondary Hyperparathyroidism in Vitamin D Receptor Deficient Mice

2020 ◽  
Vol 21 (21) ◽  
pp. 7989
Author(s):  
Barbara M. Misof ◽  
Stéphane Blouin ◽  
Jochen G. Hofstaetter ◽  
Paul Roschger ◽  
Jochen Zwerina ◽  
...  
Keyword(s):  
Vitamin D ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Receptor ◽  
Bone Mineralization ◽  
Normal Diet ◽  
Wild Type ◽  
Mineral Homeostasis ◽  
Osteocyte Lacunae ◽  
Osteocytic Osteolysis ◽  
Electron Imaging

Osteocytic osteolysis/perilacunar remodeling is thought to contribute to the maintenance of mineral homeostasis. Here, we utilized a reversible, adult-onset model of secondary hyperparathyroidism to study femoral bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) based on quantitative backscattered electron imaging. Male mice with a non-functioning vitamin D receptor (VDRΔ/Δ) or wild-type mice were exposed to a rescue diet (RD) (baseline) and subsequently to a low calcium challenge diet (CD). Thereafter, VDRΔ/Δ mice received either the CD, a normal diet (ND), or the RD. At baseline, BMDD and OLS characteristics were similar in VDRΔ/Δ and wild-type mice. The CD induced large cortical pores, osteomalacia, and a reduced epiphyseal average degree of mineralization in the VDRΔ/Δ mice relative to the baseline (−9.5%, p < 0.05 after two months and −10.3%, p < 0.01 after five months of the CD). Switching VDRΔ/Δ mice on the CD back to the RD fully restored BMDD to baseline values. However, OLS remained unchanged in all groups of mice, independent of diet. We conclude that adult VDRΔ/Δ animals on an RD lack any skeletal abnormalities, suggesting that VDR signaling is dispensable for normal bone mineralization as long as mineral homeostasis is normal. Our findings also indicate that VDRΔ/Δ mice attempt to correct a calcium challenge by enhanced osteoclastic resorption rather than by osteocytic osteolysis.

Vitamin D Deficiency and Intoxication - A concern either way

JMS SKIMS ◽  
2011 ◽  
Vol 14 (2) ◽  
pp. 40-42
Author(s):  
Muzafar Maqsood Wani ◽  
Imtiaz Ahmed Wani
Keyword(s):  
Vitamin D ◽  
Cell Growth ◽  
Bone Turnover ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Deficiency ◽  
Bone Mineralization ◽  
Normal Blood ◽  
Blood Levels ◽  
Calcium And Phosphorus ◽  
Biologic Function

Major biologic function of activated vitamin D is to maintain normal blood levels of calcium and phosphorus, thus regulating bone mineralization. Research suggests that vitamin D may help in immunomodulation, regulating cell growth and 1,4 differentiation as well as some diverse unspecified functions. Overt vitamin D deficiency leads to hypocalcaemia, secondary hyperparathyroidism and increased bone turnover, which in prolonged and severe cases may cause rickets in children and osteomalacia in elderly.... JMS 2011;14(2):40-42

scholarly journals The effectiveness of nutritional vitamin D supplementation and selective vitamin D receptor agonists treatment on secondary hyperparathyroidism in chronic kidney diseases patients

2018 ◽  
Vol 21 (2) ◽  
pp. 12-22 ◽  
Author(s):  
Lilit V. Egshatyan ◽  
Natalya G. Mokrisheva
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Receptor ◽  
Vitamin D Supplementation ◽  
Target Range ◽  
Receptor Agonists ◽  
Stage 4 ◽  
Calcium Phosphorus ◽  
Phosphorus Levels

Background: secondary hyperparathyroidism (SHPT) is an early complication of chronic kidney disease (CKD). Maintaining the level of 25(OH)D and parathyroid hormone concentrations in the target range reduce its associated complications (fractures and cardiovascular calcification). Aims: to examine the effectiveness of vitamin D supplementation and selective vitamin D receptor agonists treatment on SHPT in CKD. Material and methods: prospective observational study to evaluate the efficacy and safety of vitamin D therapy SHPT in 54 in patients with CKD. The first phase (24 weeks) – treatment of suboptimal 25-hydroxycalciferol (25(OH)D) levels. The second (16 weeks) – treatment colecalciferol-resistant SHPT by combination of cholecalciferol with paricalcitol. Blood samples were taken to assess parathyroid hormone (PTH), 25(OH)D, creatinine, calcium, phosphorus levels and calcium excretion. Results: After 8 weeks of cholecalciferol treatment all patients achieved 25(OH)D levels above 20 ng/ml, however 78% of patients still had SHPT. After 16 weeks, the decrease of PTH was achieved in all patients, but significantly only in patients with CKD 2 (19.2%, p< 0.01) and 3 (31%, p <0.05), compared with CKD 4 (17%, p >0.05). After 24 weeks of therapy, PTH normalized in all patients with CKD 2, in 15 (79%) with CKD 3 and in 9 (50%) patients with CKD 4. Cholecalciferol treatment resulted in a substantial increase in 25(OH)D levels with minimal or no impact on calcium, phosphorus levels and kidney function. After 24 weeks we initiated combination therapy (cholecalciferol and paricalcitol) for patients with colecalciferol-resistant SHPT (n=13). PTH levels decreased from 149.1±13.4 to 118.2±14.1 pg/ml at 8 weeks, and to 93.1±9.7 pg/ml (p <0.05) at 16 weeks of treatment. No significant differences in serum calcium, phosphorus or urinary calcium levels. Normalization of PTH was achieved in all patients with CKD 3 and in 8 patients with stage 4. One patient with CKD 4 needed an increase in paricalcitol dose. Conclusion: Cholecalciferol can be used in correcting vitamin D deficiency in patients with all stages of CKD, however, its effectiveness in reducing PTH in stage 4 is limited. Selective analogs, such as paricalcitol, were well-tolerated and effectively decreased PTH levels.

scholarly journals BSMI AND TAQI POLYMORPHISMS IN VITAMIN D RECEPTOR GENE OF TYPE 2 DIABETES MELLITUS PATIENTS FROM NORTH INDIA

2016 ◽  
Vol 9 (9) ◽  
pp. 186 ◽  
Author(s):  
Nancy Taneja ◽  
Rajesh Khadagawat ◽  
Shalini Mani
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Metabolic Diseases ◽  
Fragment Length Polymorphism ◽  
Wild Type ◽  
Significant Difference ◽  
Restriction Fragment Length

ABSTRACTObjective: Polymorphisms in vitamin D receptor (VDR) genes are known to be linked with different metabolic diseases including Type 2 diabetesmellitus (T2DM) also. However, the association of these polymorphisms is not much explored for the Indian population. To determine the prevalenceof BsmI and TaqI polymorphism in VDR gene of T2DM patients from North India.Methods: Blood samples were obtained from 100 well-characterized T2DM patients and 100 healthy controls. Genomic DNA was isolated from bloodsamples and using polymerase chain reaction/restriction fragment length polymorphism based method, the presence of these polymorphisms wasinvestigated in these samples. The data were statistically analyzed using SPSS 21.0 software.Results: For TaqI polymorphism, both the wild type (TT) and heterozygous (TC) genotype showed a significant difference between patients andcontrols (p=0.023 and p<0.001, respectively). Whereas, the frequency of CC genotype was not significantly different among these groups (p=0.506).For BsmI polymorphism also, the frequency of wild type (GG) and heterozygous (GA) genotype was significantly different in patients and controls(p=0.027 and p=0.001), respectively. However, the frequency of AA genotype was not of statistical significance in patients (p=0.071).Conclusions: The mutant alleles of TaqI and BsmI polymorphisms are known to be associated with different metabolic diseases, including diabetestoo. In our study also, there is a significant difference between the frequency of wild type and heterozygous genotype for these polymorphisms. Thissuggests that BsmI and TaqI polymorphisms may be associated with T2DM patients.Keywords: Type 2 diabetes mellitus, Polymorphism, Vitamin D receptor, Patient, Control, Restriction fragment length polymorphism.

scholarly journals The Role of Vitamin D and Vitamin D Receptor in Immunity toLeishmania majorInfection

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
James P. Whitcomb ◽  
Mary DeAgostino ◽  
Mark Ballentine ◽  
Jun Fu ◽  
Martin Tenniswood ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune Responses ◽  
Vitamin D Receptor ◽  
Leishmania Major ◽  
Active Form ◽  
Wild Type ◽  
Vitamin D Signaling ◽  
Deficient Mice ◽  
Th 1

Vitamin D signaling modulates a variety of immune responses. Here, we assessed the role of vitamin D in immunity to experimental leishmaniasis infection in vitamin D receptor-deficient mice (VDRKO). We observed that VDRKO mice on a genetically resistant background have decreasedLeishmania major-induced lesion development compared to wild-type (WT) mice; additionally, parasite loads in infected dermis were significantly lower at the height of infection. Enzymatic depletion of the active form of vitamin D mimics the ablation of VDR resulting in an increased resistance toL. major. Conversely, VDRKO or vitamin D-deficient mice on the susceptible Th2-biased background had no change in susceptibility. These studies indicate vitamin D deficiency, either through the ablation of VDR or elimination of its ligand, 1,25D3, leads to an increase resistance toL. majorinfection but only in a host that is predisposed for Th-1 immune responses.

scholarly journals Intestinal Resistance to 1,25 Dihydroxyvitamin D in Mice Heterozygous for the Vitamin D Receptor Knockout Allele

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1396-1402 ◽  
Author(s):  
Yurong Song ◽  
James C. Fleet
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Time Course ◽  
Transient Receptor Potential ◽  
Gene Knockout ◽  
Mrna Levels ◽  
Wild Type ◽  
Calcium Diet ◽  
Low Calcium Diet ◽  
Low Calcium

We tested the hypothesis that low vitamin D receptor (VDR) level causes intestinal vitamin D resistance and intestinal calcium (Ca) malabsorption. To do so, we examined vitamin D regulated duodenal Ca absorption and gene expression [transient receptor potential channel, vallinoid subfamily member 6 (TRPV6), 24-hydroxylase, calbindin D9k (CaBP) mRNA, and CaBP protein] in wild-type mice and mice with reduced tissue VDR levels [i.e. heterozygotes for the VDR gene knockout (HT)]. Induction of 24-hydroxylase mRNA levels by 1,25 dihydroxyvitamin D3 [1,25(OH)2 D3] injection was significantly reduced in the duodenum and kidney of HT mice in both time-course and dose-response experiments. TRPV6 and CaBP mRNA levels in duodenum were significantly induced after 1,25(OH)2 D3 injection, but there was no difference in response between wild-type and HT mice. Feeding a low-calcium diet for 1 wk increased plasma PTH, renal 1α-hydroxylase (CYP27B1) mRNA level, and plasma 1,25(OH)2 D3, and this response was greater in HT mice (by 88, 55, and 37% higher, respectively). In contrast, duodenal TRPV6 and CaBP mRNA were not higher in HT mice fed the low-calcium diet. However, the response of duodenal Ca absorption and CaBP protein to increasing 1,25(OH)2 D3 levels was blunted by 40% in HT mice. Our data show that low VDR levels lead to resistance of intestinal Ca absorption to 1,25(OH)2 D3, and this resistance may be due to a role for the VDR (and VDR level) in the translation of CaBP.

scholarly journals Dietary Phosphorus Restriction Reverses the Impaired Bone Mineralization in Vitamin D Receptor Knockout Mice

Endocrinology ◽  
2001 ◽  
Vol 142 (1) ◽  
pp. 494-497 ◽  
Author(s):  
Ritsuko Masuyama ◽  
Yumi Nakaya ◽  
Shinya Tanaka ◽  
Hiroshi Tsurukami ◽  
Toshitaka Nakamura ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Knockout Mice ◽  
Bone Mineralization ◽  
Dietary Phosphorus

scholarly journals The Vitamin D Receptor Regulates Tissue Resident Macrophage Response to Injury

Endocrinology ◽  
2016 ◽  
Vol 157 (10) ◽  
pp. 4066-4075 ◽  
Author(s):  
Lige Song ◽  
Garyfallia Papaioannou ◽  
Hengguang Zhao ◽  
Hilary F. Luderer ◽  
Christine Miller ◽  
...  
Keyword(s):  
Vitamin D ◽  
Wound Healing ◽  
Vitamin D Receptor ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Dermal Fibroblasts ◽  
Wild Type ◽  
Macrophage Response ◽  
Protein Levels ◽  
Inflammatory Phase

Ligand-dependent actions of the vitamin D receptor (VDR) play a pleiotropic role in the regulation of innate and adaptive immunity. The liganded VDR is required for recruitment of macrophages during the inflammatory phase of cutaneous wound healing. Although the number of macrophages in the granulation tissue 2 days after wounding is markedly reduced in VDR knockout (KO) compared with wild-type mice, VDR ablation does not alter macrophage polarization. Parabiosis studies demonstrate that circulatory chimerism with wild-type mice is unable to rescue the macrophage defect in the wounds of VDR KO mice and reveal that wound macrophages are of local origin, regardless of VDR status. Wound cytokine analyses demonstrated a decrease in macrophage colony-stimulating factor (M-CSF) protein levels in VDR KO mice. Consistent with this, induction of M-CSF gene expression by TGFβ and 1,25-dihydroxyvitamin D was impaired in dermal fibroblasts isolated from VDR KO mice. Because M-CSF is important for macrophage self-renewal, studies were performed to evaluate the response of tissue resident macrophages to this cytokine. A decrease in M-CSF induced proliferation and cyclin D1 expression was observed in peritoneal resident macrophages isolated from VDR KO mice, suggesting an intrinsic macrophage abnormality. Consistent with this, wound-healing assays in mice with macrophage-specific VDR ablation demonstrate that a normal wound microenvironment cannot compensate for the absence of the VDR in macrophages and thus confirm a critical role for the macrophage VDR in the inflammatory response to injury.

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