scholarly journals Identification the Synergistic Effect of Immune-Related lncRNA KIAA0125 and Vitamin D Metabolism Related Gene CYP24A1 in Periodontitis

Author(s):  
Yang Li ◽  
Ruixue Li ◽  
Ying Wu ◽  
Chan-Juan Gong ◽  
XiaoJun Ding

Abstract Background: Periodontitis is a chronic infectious disease characterized by gingival inflammation and progressive destruction of alveolar bone. The interaction of periodontal plaque microorganisms and host immune response affects the process and progression of periodontitis. However, the specific mechanisms and biomarkers involved in periodontitis remain to be further studied. Methods: In the present research, we explored the expression profile data of differentially expressed lncRNAs and immune-related mRNAs and constructed the competing endogenous RNAs (ceRNA) network. The CIBERSORT analysis was used to infer the composition of 22 immune cells in periodontitis. The genes in ceRNA network were further screened by weighted gene co-expression network analysis (WGCNA), transcriptomic sequencing and PCR. Results: Our results indicated that a total of 1 lncRNA (KIAA0125), 3 miRNAs (miR-449c-5p, miR-125a-5p and miR-125b-5p) and 2 mRNAs (CYP24A1, BTG2) were involved in establishing the ceRNA network for periodontitis. The expression of KIAA0125 was highly correlated with plasma cells and B cells markers. The WGCNA and transcriptomic sequencing screened out the key gene as the vitamin D metabolic enzyme CYP24A1. The experimental results showed both KIAA0125 and CYP24A1 were highly expressed in the periodontitis gingival tissues. In vitro experiments, the expression of KIAA0125 in human periodontal ligament cells (hPDLCs) were increased after the treatment of lipopolysaccharide and 1,25-dihydroxyvitamin D3 (1,25D) (P < 0.05). In addition, we found that 1,25D could alleviate the inflammation of LPS-induced hPDLCs, while the increased expression of KIAA0125 and CYP24A1 would antagonize the anti-inflammatory effect. Conclusion: In conclusion, immune-related lncRNA KIAA0125 and vitamin D metabolism related gene CYP24A1 can be used as potential diagnostic indicators of periodontitis.

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1195-1195
Author(s):  
Carlo Foresta ◽  
Giacomo Strapazzon ◽  
Luca De Toni ◽  
Lisa Perilli ◽  
Antonella Di Mambro ◽  
...  

Abstract Working Hypothesis: Mutations in the CYP2R1 gene, highly expressed in the testis and encoding vitamin D 25-hydroxylase, result in a vitamin D deficiency and a defective calcium homeostasis leading to rickets. Objective: Our aim was to investigate CYP2R1 expression in pathological testis samples and relate this to vitamin D metabolism in testiculopathic patients. Design, Patients, Setting: Testis samples for in vitro study and 98 young men were transversally evaluated at Padova's Center for Male Gamete Cryopreservation. Methods: CYP2R1 mRNA expression and protein production were evaluated by quantitative RT-PCR, Western blot analysis, and immunofluorescence. Hormonal and bone-marker levels, and bone densitometry by dual-energy x-ray absorptiometry, were determined in patients with Sertoli-cell-only syndrome and severe hypospermatogenesis. Results: We found a lower gene and protein expression of CYP2R1 in samples with hypospermatogenesis and Sertoli-cell-only syndrome (P &lt; 0.05) and a colocalization with INSL-3, a Leydig cell marker, at immunofluorescence. In all testiculopathic patients 25-hydroxyvitamin D levels were significantly lower and PTH levels higher compared to controls (P &lt; 0.05). Furthermore, testiculopathic patients showed osteopenia and osteoporosis despite normal testosterone levels compared with controls both with increased bone-marker levels and altered dual-energy x-ray absorptiometry in the femoral neck and lumbar spine (for all parameters, P &lt; 0.05). Conclusions: Our data show an association between testiculopathy and alteration of the bone status, despite unvaried androgen and estrogen levels and no other evident cause of vitamin D reduction. Further studies in larger cohorts are needed to confirm our results.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sarah A. Howles ◽  
Akira Wiberg ◽  
Michelle Goldsworthy ◽  
Asha L. Bayliss ◽  
Anna K. Gluck ◽  
...  

AbstractKidney stone disease (nephrolithiasis) is a major clinical and economic health burden with a heritability of ~45–60%. We present genome-wide association studies in British and Japanese populations and a trans-ethnic meta-analysis that include 12,123 cases and 417,378 controls, and identify 20 nephrolithiasis-associated loci, seven of which are previously unreported. A CYP24A1 locus is predicted to affect vitamin D metabolism and five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. In a validation cohort of only nephrolithiasis patients, the CYP24A1-associated locus correlates with serum calcium concentration and a number of nephrolithiasis episodes while the DGKD-associated locus correlates with urinary calcium excretion. In vitro, DGKD knockdown impairs CaSR-signal transduction, an effect rectified with the calcimimetic cinacalcet. Our findings indicate that studies of genotype-guided precision-medicine approaches, including withholding vitamin D supplementation and targeting vitamin D activation or CaSR-signaling pathways in patients with recurrent kidney stones, are warranted.


2013 ◽  
Vol 66 (5-6) ◽  
pp. 259-262
Author(s):  
Goran Marusic ◽  
Dimitrije Jeremic ◽  
Sasa Vojinov ◽  
Natasa Filipovic ◽  
Milan Popov

In addition to the metabolic role of vitamin D, which is well known and clearly defined, there have been many hypotheses regarding its anti-proliferative and pro-apoptotic role. Epidemiology and Significance of Prostate Cancer. Prostate cancer is the second most common malignancy in men. Long period of cancerogenesis, available tumor markers and high incidence make this cancer ideal for preventive measures. Physiological Role of Vitamin D and its Effect on Prostate Cancer Cells. In vitro and in vivo studies have shown the anti-proliferative and pro-apoptopic role of vitamin D. Disorders of vitamin D metabolism are noted in vitamin D gene level, vitamin D receptor, vitamin D responsive elements and androgen receptors. We present the most important effect of those changes on vitamin D metabolism. Conclusion. Available studies on vitamin D level in serum, prostate tissue, observed activity of vitamin D enzymes and genetic changes give us only a slight insight into the basic mechanisms of vitamin D action in the development of prostate cancer; therefore, further investigations are needed.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
May A. Beydoun ◽  
Sharmin Hossain ◽  
Salman M. Tajuddin ◽  
Jose A. Canas ◽  
Marie Kuczmarski ◽  
...  

1980 ◽  
Vol 239 (6) ◽  
pp. G480-G484 ◽  
Author(s):  
U. Gafter ◽  
J. A. Kraut ◽  
D. B. Lee ◽  
V. Silis ◽  
M. W. Walling ◽  
...  

To investigate the effect of metabolic acidosis on intestinal calcium (Ca) and phosphorus (P) absorption and vitamin D metabolism, metabolic balance studies and in vitro gut sac uptake of 45Ca and [32P]phosphate were performed in rats maintained on low-Ca and moderately low-P diet and fed NH4Cl for 3 or 9 days and pair-fed controls. Plasma 1,25(OH)2D concentration was measured in the rats fed NH4Cl for 9 days and their controls. Net Ca and P absorption was 87–92% in the acidotic rats and did not differ from control. Moreover, gut sac uptakes of 45Ca and [32P]phosphate were not different from control. Plasma 1,25(OH)2D was higher in the ammonium chloride-fed rats than in controls (213 +/- 44 vs. 110 +/- 12 pg/ml), and serum P was lower in the acidotic animals (4.6 +/- 0.7 vs. 7.6 +/- 0.3 mg/dl). These data indicate that metabolic acidosis does not depress the augmented intestinal absorption of calcium and phosphorus noted during their dietary deprivation nor reduce the plasma level of 1,25(OH)2D.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 365-365
Author(s):  
Cai-Xia Zhang

Abstract Objectives Vitamin D has anticarcinogenic properties. Vitamin D metabolism-related gene polymorphisms can influence vitamin D levels and its impact on carcinogenesis. This study aimed to explore the independent and combined effects of dietary vitamin D and vitamin D metabolism-related gene polymorphisms on colorectal cancer risk in a Chinese population. Methods Incident cases with histologically confirmed colorectal cancer, and sex and age-matched controls were recruited in this ongoing case-control study. Of them, 488 cases and 496 controls were both successfully interviewed and collected blood samples. Vitamin D intake was assessed by a validated food frequency questionnaire. Genotyping was performed for CYP2R1 rs10741657, CYP2R1 rs12794714, CYP24A1 rs6013897, CYP24A1 rs6068816, CYP27B1 rs4646536 and GC rs7041 by using an improved multiplex ligation detection reaction (iMLDR) technique. Unconditional multivariable logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI) after adjusting for various confounders. Results Higher intake of dietary vitamin D was associated with 47% reduction in colorectal cancer with OR of 0.53 (95% CI: 0.34, 0.82) for the highest quartile (vs. lowest quartile) intake. Compared with persons with CYP24A1 rs6068816 CC genotype, lower risk of colorectal cancer was observed among carriers of TT genotype (OR = 0.57, 95%CI 0.36, 0.89). No significant association was found between CYP2R1 rs10741657, CYP2R1 rs12794714, CYP24A1 rs6013897, CYP27B1 rs4646536, GC rs7041 and colorectal cancer risk. No significant interaction was observed between dietary vitamin D intake and six examined single nucleotide polymorphisms on the risk of colorectal cancer. Conclusions Our study supports a protective effect of high intake of dietary vitamin D on colorectal cancer. CYP24A1 rs6068816 TT genotype was significantly associated with a decreased risk of colorectal cancer. No interaction was observed between dietary vitamin D intake and six examined single nucleotide polymorphisms in a Chinese population. Funding Sources Guangdong Natural Science Foundation (No: 2019A1515011931).


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Francesca Colonese ◽  
Antonio Simone Laganà ◽  
Elisabetta Colonese ◽  
Vincenza Sofo ◽  
Francesca Maria Salmeri ◽  
...  

The traditionally recognized role of vitamin D consists in the regulation of bone metabolism and calcium-phosphorus homeostasis but recently a lot of in vitro and in vivo studies recognized several “noncalcemic” effects of vitamin D metabolites. Accumulating evidence suggests that the metabolic pathways of this vitamin may play a key role in the developing of gynaecological/obstetric diseases. VDR-mediated signalling pathways and vitamin D levels seem to (deeply) affect the risk of several gynaecological diseases, such as polycystic ovary syndrome (PCOS), endometriosis, and ovarian and even breast cancer. On the other hand, since also the maternal-fetal unit is under the influence of vitamin D, a breakdown in its homeostasis may underlie infertility, preeclampsia, and gestational diabetes mellitus (GDM). According to our literature review, the relationship between vitamin D and gynaecological/obstetric diseases must be replicated in future studies which could clarify the molecular machineries behind their development. We suggest that further investigation should take into account the different serum levels of this vitamin, the several actions which arise from the binding between it and its receptor (taking into account its possible polymorphism), and finally the interplay between vitamin D metabolism and other hormonal and metabolic pathways.


1988 ◽  
Vol 254 (2) ◽  
pp. E150-E154
Author(s):  
T. O. Carpenter ◽  
M. L. Pendrak ◽  
C. S. Anast

Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. We investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D3 [25(OH)D3] resulted in reduced 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in copper-intoxicated rats. In vitro 25(OH)D-1 alpha-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondria from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH)2D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease.


1988 ◽  
Vol 255 (5) ◽  
pp. E702-E707 ◽  
Author(s):  
J. Fox

In vitro, verapamil inhibits duodenal Ca absorption, parathyroid hormone (PTH) secretion, and PTH-stimulated bone resorption. This study was designed to determine if any effects of chronic oral verapamil treatment on PTH secretion-action are reflected by changes in vitamin D metabolism, duodenal Ca absorption, and bone Ca content. Rats (100 g) received verapamil in the drinking water at doses of 4, 20, or 100 mumol.kg-1.day-1 for 2 wk. Verapamil administration did not significantly affect growth, plasma Ca or phosphate, or bone Ca content. However, verapamil treatment was associated with a dose-dependent 90% increase in plasma PTH levels. The elevated PTH was accompanied by a 22% decrease in 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels, such that there was a significant negative correlation (r = -0.52; P less than 0.01) between PTH and 1,25(OH)2D3 levels. Despite the decreased plasma 1,25(OH)2D3 levels, verapamil treatment was associated with a dose-dependent increase in duodenal Ca absorption. The increased Ca absorption did not seem to be caused by a verapamil-induced increased intestinal sensitivity to 1,25(OH)2D3, since verapamil-treated vitamin D-deficient rats showed the same absorptive response to administered 1,25(OH)2D3 as untreated rats. Thus chronic oral verapamil treatment induces an apparent PTH resistance but does not appear to have major effects on overall Ca homeostasis in young male rats.


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