scholarly journals The Vitamin D Receptor in Osteoblast-Lineage Cells Is Essential for the Proresorptive Activity of 1α,25(OH)2D3 In Vivo

Endocrinology ◽  
2020 ◽  
Vol 161 (11) ◽  
Author(s):  
Tomoki Mori ◽  
Kanji Horibe ◽  
Masanori Koide ◽  
Shunsuke Uehara ◽  
Yoko Yamamoto ◽  
...  
Keyword(s):  
Vitamin D ◽  
Body Weight ◽  
Bone Resorption ◽  
Vitamin D Receptor ◽  
The Body ◽  
Conditional Knockout ◽  
High Dose ◽  
Type I ◽  
Wild Type ◽  
Osteoblast Lineage

Abstract We previously reported that daily administration of a pharmacological dose of eldecalcitol, an analog of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], increased bone mass by suppressing bone resorption. These antiresorptive effects were found to be mediated by the vitamin D receptor (VDR) in osteoblast-lineage cells. Using osteoblast-lineage-specific VDR conditional knockout (Ob-VDR-cKO) mice, we examined whether proresorptive activity induced by the high-dose 1α,25(OH)2D3 was also mediated by VDR in osteoblast-lineage cells. Administration of 1α,25(OH)2D3 (5 μg/kg body weight/day) to wild-type mice for 4 days increased the number of osteoclasts in bone and serum concentrations of C-terminal crosslinked telopeptide of type I collagen (CTX-I, a bone resorption marker). The stimulation of bone resorption was concomitant with the increase in serum calcium (Ca) and fibroblast growth factor 23 (FGF23) levels, and decrease in body weight. This suggests that a toxic dose of 1α,25(OH)2D3 can induce bone resorption and hypercalcemia. In contrast, pretreatment of wild-type mice with neutralizing anti-receptor activator of NF-κB ligand (RANKL) antibody inhibited the 1α,25(OH)2D3-induced increase of osteoclast numbers in bone, and increase of CTX-I, Ca, and FGF23 levels in serum. The pretreatment with anti-RANKL antibody also inhibited the 1α,25(OH)2D3-induced decrease in body weight. Consistent with observations in mice conditioned with anti-RANKL antibody, the high-dose administration of 1α,25(OH)2D3 to Ob-VDR-cKO mice failed to significantly increase bone osteoclast numbers, serum CTX-I, Ca, or FGF23 levels, and failed to reduce the body weight. Taken together, this study demonstrated that the proresorptive, hypercalcemic, and toxic actions of high-dose 1α,25(OH)2D3 are mediated by VDR in osteoblast-lineage cells.

scholarly journals Vitamin D Supplementation in Laboratory-Bred Mice: An In Vivo Assay on Gut Microbiome and Body Weight

2020 ◽  
Vol 13 ◽  
pp. 117863612094529
Author(s):  
Lorina Ineta Badger-Emeka ◽  
Zainab Yaseen AlJaziri ◽  
Cereen Fahad Almulhim ◽  
Asma Saleh Aldrees ◽  
Zainab Hamzah AlShakhs ◽  
...  
Keyword(s):  
Vitamin D ◽  
Body Weight ◽  
Vitamin D Supplementation ◽  
The Body ◽  
Automated System ◽  
Control Group ◽  
High Dose ◽  
Bacterial Colony ◽  
Normal Dose ◽  
Significant Difference

Saudi Arabia is in a tropical geographical region with a population that has access to adequate diet. There is, however, a high level of vitamin D deficiency in the Kingdom, comorbid with other disease. There is the postulation of a correlation between a healthy gut microbiota and balanced levels of serum vitamin D. This investigation looks into the effect of vitamin D supplementation on the gut flora of laboratory-bred mice as well as any possible association on body weight. BALB/C mice weighing between 34 and 35.8 g were divided into 4 groups and placed on daily doses of vitamin D of 3.75 µg (low dose), 7.5 µg (normal dose), and 15 µg (high dose). The fourth group was the control group that did not receive any supplementation with vitamin D. Body weights were monitored on weekly basis, while faecal samples from the rectum were obtained for microbial culturing and the monitoring of bacterial colony count using the Vitek 2 Compact automated system (BioMerieux, Marcy-l’Etoile, France) according to manufacturer’s guidelines. The data presented as mean ± SD, while significant differences were determined with 2-way analysis of variance in comparing differences within and between treatment groups. The different doses of vitamin D showed varying effects on the body weight and gut microbial colonies of the mice. There was a highly significant difference between the control, 15 µg (high), and 7.5 µg (normal) dose groups. This is suggestive that supplementation with vitamin D could a role in the gut microbial flora in the gut which could reflect in changes in body weight.

scholarly journals Macrophage secretion of miR-106b-5p causes renin-dependent hypertension

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
J. Oh ◽  
S. J. Matkovich ◽  
A. E. Riek ◽  
S. M. Bindom ◽  
J. S. Shao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vitamin D ◽  
Endoplasmic Reticulum ◽  
Vitamin D Receptor ◽  
Conditional Knockout ◽  
Macrophage Infiltration ◽  
Wild Type ◽  
Induced Hypertension ◽  
Vitamin D Signaling ◽  
Inflammatory Macrophage

Abstract Myeloid cells are known mediators of hypertension, but their role in initiating renin-induced hypertension has not been studied. Vitamin D deficiency causes pro-inflammatory macrophage infiltration in metabolic tissues and is linked to renin-mediated hypertension. We tested the hypothesis that impaired vitamin D signaling in macrophages causes hypertension using conditional knockout of the myeloid vitamin D receptor in mice (KODMAC). These mice develop renin-dependent hypertension due to macrophage infiltration of the vasculature and direct activation of renal juxtaglomerular (JG) cell renin production. Induction of endoplasmic reticulum stress in knockout macrophages increases miR-106b-5p secretion, which stimulates JG cell renin production via repression of transcription factors E2f1 and Pde3b. Moreover, in wild-type recipient mice of KODMAC/miR106b−/− bone marrow, knockout of miR-106b-5p prevents the hypertension and JG cell renin production induced by KODMAC macrophages, suggesting myeloid-specific, miR-106b-5p-dependent effects. These findings confirm macrophage miR-106b-5p secretion from impaired vitamin D receptor signaling causes inflammation-induced hypertension.

Effect of ANG II type I receptor antagonist and ACE inhibitor on vitamin D receptor-null mice

2003 ◽  
Vol 285 (1) ◽  
pp. R255-R261 ◽  
Author(s):  
Juan Kong ◽  
Yan Chun Li
Keyword(s):  
Vitamin D ◽  
Receptor Antagonist ◽  
Vitamin D Receptor ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Type I ◽  
Ang Ii ◽  
Wild Type ◽  
Stimulation Of

We recently showed that vitamin D receptor (VDR) inactivation results in deregulated stimulation of the renin-angiotensin system (RAS). To address further the relation between RAS activation and the abnormalities in electrolyte and volume homeostasis, we studied the effect of the ANG II type I receptor antagonist losartan and the angiotensin-converting enzyme inhibitor captopril on VDR-null mice. Treatment with losartan or captopril normalized the water intake and urine excretion of VDR-null mice. However, the increase in salt excretion in VDR-null mice was not affected by either drug, suggesting that this abnormality is independent of the RAS. Northern blot and immunohistochemical analyses revealed that both drugs caused a drastic stimulation of renin expression in wild-type and VDR-null mice, but renin expression remained much higher in the treated VDR-null mice than in the treated wild-type mice, suggesting that the ANG II feedback mechanism remains intact in the mutant mice. These data firmly established a causative relation between RAS overstimulation and the abnormal volume homeostasis in VDR-null mice and demonstrated that vitamin D repression of renin expression is independent of the ANG II feedback regulation in vivo.

scholarly journals The effect of a high-protein, high-sodium diet on calcium and bone metabolism in postmenopausal women and its interaction with vitamin D receptor genotype

2004 ◽  
Vol 91 (1) ◽  
pp. 41-51 ◽  
Author(s):  
Mary Harrington ◽  
Teresa Bennett ◽  
Jette Jakobsen ◽  
Lars Ovesen ◽  
Christine Brot ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Bone Metabolism ◽  
Postmenopausal Women ◽  
Vitamin D Receptor ◽  
Type I Collagen ◽  
High Protein ◽  
Type I ◽  
Dietary Regimen ◽  
High Sodium

The influence of a high-Na, high-protein (calciuric) diet on Ca and bone metabolism was investigated in postmenopausal women (aged 50–67 years) who were stratified by vitamin D receptor (VDR) genotype. In a crossover trial, twenty-four women were randomly assigned to a diet high in protein (90 g/d) and Na (180 mmol/d) or a diet adequate in protein (70 g/d) and low in Na (65 mmol/d) for 4 weeks, followed by crossover to the alternative dietary regimen for a further 4 weeks. Dietary Ca intake was maintained at usual intakes (about 20 mmol (800 mg)/d). Urinary Na, K, Ca, N and type I collagen cross-linked N-telopeptide (NTx; a marker of bone resorption), plasma parathyroid hormone (PTH), serum 25-hydroxycholecalciferol (25(OH)D3), 1,25-dihydroxycholecalciferol (1,25(OH)2D3), osteocalcin and bone-specific alkaline phosphatase (B-Alkphase) were measured in 24 h urine samples and fasting blood samples collected at the end of each dietary period. The calciuric diet significantly (P<0·05) increased mean urinary Na, N, K, Ca and NTx (by 19 %) compared with the basal diet, but had no effect on circulating 25(OH)D3, 1,25(OH)2D3, PTH, osteocalcin or B-Alkphase in the total group (n 24). There were no differences in serum markers or urinary minerals between the basal and calciuric diet in either VDR genotype groups. While the calciuric diet significantly increased urinary NTx (by 25·6 %, P<0·01) in the f+ VDR group (n 10; carrying one or more (f) Fok I alleles), it had no effect in the f− VDR group (n 14; not carrying any Fok I alleles). It is concluded that the Na- and protein-induced urinary Ca loss is compensated for by increased bone resorption and that this response may be influenced by VDR genotype.

Roux-en-Y Gastrointestinal Bypass Promotes Activation of TGR5 and Peptide YY

2020 ◽  
Vol 20 (8) ◽  
pp. 1262-1267
Author(s):  
Haojun Yang ◽  
Hanyang Liu ◽  
YuWen Jiao ◽  
Jun Qian
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Metabolic Diseases ◽  
Peptide Yy ◽  
The Body ◽  
Wild Type ◽  
L Cells ◽  
Body Weights ◽  
Gastrointestinal Bypass ◽  
G Protein Coupled

Background: G protein-coupled bile acid receptor (TGR5) is involved in a number of metabolic diseases. The aim of this study was to identify the role of TGR5 after Roux-en-Y gastric bypass (GBP). Methods: Wild type and TGR5 knockout mice (tgr5-/-) were fed a high-fat diet (HFD) to establish the obesity model. GBP was performed. The changes in body weight and food intake were measured. The levels of TGR5 and peptide YY (PYY) were evaluated by RT-PCR, Western blot, and ELISA. Moreover, the L-cells were separated from wild type and tgr5-/- mice. The levels of PYY in L-cells were evaluated by ELISA. Results: The body weights were significantly decreased after GBP in wild type mice (p<0.05), but not tgr5-/- mice (p>0.05). Food intake was reduced after GBP in wild type mice, but also not significantly affected in tgr5-/- mice (p>0.05). The levels of PYY were significantly increased after GBP compared with the sham group (p<0.05); however, in tgr5-/- mice the expression of PYY was not significantly affected (p>0.05). After INT-777 stimulation in L-cells obtained from murine intestines, the levels of PYY were significantly increased in L-cells tgr5+/+ (p<0.05). Conclusion: Our study suggests that GBP up-regulated the expression of TGR5 in murine intestines, and increased the levels of PYY, which further reduced food intake and decreased the body weight.

scholarly journals Cardiorespiratory Fitness and Diet Quality Profile of the Lithuanian Team of Deaf Women’s Basketball Players

2020 ◽  
Vol 17 (18) ◽  
pp. 6749
Author(s):  
Marius Baranauskas ◽  
Valerija Jablonskienė ◽  
Jonas Algis Abaravičius ◽  
Rimantas Stukas
Keyword(s):  
Vitamin D ◽  
Body Composition ◽  
Body Weight ◽  
Cardiorespiratory Fitness ◽  
Female Athletes ◽  
The Body ◽  
Physical Working Capacity ◽  
Working Capacity ◽  
Women's Basketball ◽  
Basketball Team

There are about 466 million people with hearing impairments in the world. The scientific literature does not provide sufficient data on the actual nutrition and other variables of professional deaf athletes. The objectives of this study were to investigate and evaluate the body composition, the physical working capacity, the nutrition intake, and the blood parameters of iron and vitamin D in the Lithuanian high-performance deaf women’s basketball team players. The female athletes (n = 14) of the Lithuanian deaf basketball team aged 26.4 ± 4.5 years were recruited for an observational cross-sectional study. A 7-day food recall survey method was used to investigate their actual diet. The measurements of the body composition were performed using the BIA (bioelectrical impedance analysis) tetra-polar electrodes. In order to assess the cardiorespiratory and aerobic fitness levels of athletes, ergo-spirometry (on a cycle ergometer) was used to measure the peak oxygen uptake (VO2peak) and the physical working capacity at a heart rate of 170 beats per minute (PWC170). The athletes’ blood tests were taken to investigate the red blood cells, hemoglobin, 25-hydroxyvitamin D, ferritin, transferrin, iron concentrations, and total iron-binding capacity (TIBC). The consideration of the VO2peak (55.9 ± 6.1 mL/min/kg of body weight, 95% CI: 51.8, 58.9) and the low VO2peak (56–60 mL/min/kg of body weight) (p = 0.966) in the deaf women’s basketball team players revealed no differences. For the deaf female athletes, the PWC170 was equal to 20.3 ± 2.0 kgm/min/kg of body weight and represented only the average aerobic fitness level. The carbohydrate and protein intakes (5.0 ± 1.3 and 1.3 ± 0.3 g/kg of body weight, respectively) met only the minimum levels recommended for athletes. The fat content of the diet (38.1 ± 4.1% of energy intake) exceeded the maximum recommended content (35% of energy intake) (p = 0.012). The mean blood serum concentrations of 25(OH)D and ferritin (24.1 ± 6.6 nmol/L and 11.0 ± 4.1 µg/L, respectively) predicted vitamin D and iron deficits in athletes. Female athletes had an increased risk of vitamin D and iron deficiencies. Regardless of iron deficiency in the body, the better cardiorespiratory fitness of the deaf female athletes was essentially correlated with the higher skeletal muscle mass (in terms of size) (r = 0.61, p = 0.023), the lower percentage of body fat mass (r = −0.53, p = 0.049), and the reduced intake of fat (r = −0.57, p = 0.040).

One-generation reproduction toxicity study of Dithane M-45 (mancozeb) and lead acetate

2002 ◽  
Vol 50 (3) ◽  
pp. 365-371 ◽  
Author(s):  
L. Várnagy ◽  
P. Budai ◽  
E. Molnár ◽  
Keyword(s):  
Body Weight ◽  
Lead Acetate ◽  
Clinical Symptoms ◽  
Reproductive Toxicity ◽  
The Body ◽  
High Dose ◽  
Lactation Period ◽  
Treatment Groups ◽  
Body Weight Increase ◽  
Dose Levels

The reproductive toxicity of lead acetate and of a fungicide formulation (Dithane M-45) containing 80% mancozeb was studied on rats. Lead acetate was applied in the feed in the following dose groups: control, 1,000, 5,000 and 10,000 mg/kg of diet. The three treatment groups received, in addition to the above doses of lead acetate, 4,500 mg/kg Dithane M-45 in the diet. The method was based on the OECD Guideline for Testing of Chemicals No. 415 (1981). Clinical symptoms and mortality were not found in the parent generation. The body weight of female animals decreased significantly before the pregnancy period. This tendency was also seen in males after the combination treatment. At the two high dose levels a remarkable body weight increase was seen in the female animals during the lactation period. As a result of treatment, decreased body weight of offspring was measured during the lactation period. No gross pathological changes were seen. Histological examination showed general tubulonephrosis in the experimental animals. It can be established that the administration of Dithane M-45 did not enhance the reproductive toxicity of lead acetate.

Exacerbated febrile responses to LPS, but not turpentine, in TNF double receptor-knockout mice

1997 ◽  
Vol 272 (2) ◽  
pp. R563-R569 ◽  
Author(s):  
L. R. Leon ◽  
W. Kozak ◽  
J. Peschon ◽  
M. J. Kluger
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Motor Activity ◽  
Knockout Mice ◽  
Low Dose ◽  
Late Phase ◽  
High Dose ◽  
Wild Type ◽  
Inflammatory Stimuli ◽  
Necrosis Factor

We examined the effects of injections of systemic [lipopolysaccharide (LPS), 2.5 mg/kg or 50 pg/kg ip] or local (turpentine, 100 microl sc) inflammatory stimuli on fever, motor activity, body weight, and food intake in tumor necrosis factor (TNF) double receptor (TNFR)-knockout mice. A high dose of LPS resulted in exacerbated fevers in TNFR-knockout mice compared with wild-type mice for the early phase of fever (3-15 h); the late phase of fever (16-24 h) and fevers to a low dose of LPS were similar in both groups. Motor activity, body weight, and food intake were similarly reduced in both groups of mice after LPS administration. In response to turpentine, TNFR-knockout and wild-type mice developed virtually identical responses to all variables monitored. These results suggest that 1) TNF modulates fevers to LPS dose dependently, 2) TNF does not modulate fevers to a subcutaneous injection of turpentine, and 3) knockout mice may develop cytokine redundancy in the regulation of the acute phase response to intraperitoneally injected LPS or subcutaneously injected turpentine.

scholarly journals 1,25-Dihydroxy-19-nor-vitamin D2, a Vitamin D Analog with Reduced Bone Resorbing Activity In Vitro

2000 ◽  
Vol 11 (10) ◽  
pp. 1857-1864
Author(s):  
L. SHANNON HOLLIDAY ◽  
STEPHEN L. GLUCK ◽  
EDUARDO SLATOPOLSKY ◽  
ALEX J. BROWN
Keyword(s):  
Vitamin D ◽  
Acid Phosphatase ◽  
Bone Resorption ◽  
Vitamin D Receptor ◽  
Intrinsic Activity ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mouse Bone Marrow ◽  
Bone Resorbing Activity

Abstract. 1,25-Dihydroxy-19-nor-vitamin D2 (19-norD2), a new analog of 1,25(OH)2D3, suppresses parathyroid hormone in renal failure patients and in uremic rats but has less calcemic activity than 1,25(OH)2D3. Although 19-norD2 has high affinity for the vitamin D receptor and similar pharmacokinetics to those of 1,25(OH)2D3, it has much less bone resorbing activity in vivo. The intrinsic activity of 19-norD2 on osteoclastogenesis and activation of bone resorption in mouse bone marrow cultures was examined to determine the mechanism involved. 19-norD2 and 1,25(OH)2D3 (10 nM) were equivalent in stimulating the formation and maintenance of large multinucleated, tartrate-resistant acid phosphatase-positive cells. However, the amount of bone resorbed by osteoclasts stimulated by 10 nM 19-norD2, as measured by pit-forming assays, was reduced 62% compared with 10 nM 1,25(OH)2D3-stimulated osteoclasts (P < 0.05). This difference could not be attributed to enhanced catabolism or to downregulated vitamin D receptor. The rate of degradation of 19-norD2 in cultures was approximately 20% greater than 1,25(OH)2D3, not enough to account for the different effects on bone resorption. The VDR levels were identical in cultures that were treated with 19-norD2 and 1,25(OH)2D3. In summary, 19-norD2 is less effective than 1,25(OH)2D3 in stimulating mouse marrow osteoclasts to resorb bone. The reason for this difference is not clear but seems to involve the late maturation and/or activation of osteoclasts as the number of pits produced by each tartrate-resistant acid phosphatase-positive cell is reduced under stimulation by 19-norD2 compared with 1,25(OH)2D3.

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