Volume 8 · Number 4 · December 2016
- Effect of RANK/RANKL/OPG pathway on bone demineralization and vascular calcification in chronic kidney disease [105-114]
- The association of MMP1 1G>2G polymorphism with aortic valve calcification [115-120]
- Functional study of promoter gene polymorphisms of sclerostin [121-126]
- Prevalence of low levels of vitamin D in patients with breast cancer who live in Northern latitudes 21-22º [127-133]
Cardiovascular complications are among the most important clinical challenges in patients with chronic kidney failure (CKF). These are frequent processes that present high morbidity and mortality. As an example, around 50% of patients with terminal CRF die from this disease 1.read more
Effect of RANK/RANKL/OPG pathway on bone demineralization and vascular calcification in chronic kidney disease
Introduction: In cases of chronic kidney disease (CKD), bone and mineral metabolism changes occur which favor soft tissue calcification. Alterations in the RANK/RANKL/OPG system could also favor vascular calcification, a major cause of morbidity and mortality in CKD.
Objective: In an in vivo experimental model of chronic renal failure progression, we assess the effect of CKD on vascular calcification and bone loss correlating these changes in the RANK/RANKL/OPG pathway. An in vitro system was used to confirm findings.
Material and Methods: Two models of vascular calcification were used: an in vivo rat model with chronic renal failure fed on a diet with different phosphorus content, and an in vitro model in vascular smooth muscle cells (VSMC) subjected to different calcifying stimuli.
Results: At 20 weeks, 50% of animals with a diet high in phosphorus presented aortic calcification accompanied by increased aortic expression of RANKL. In contrast, OPG decreased probably as a consequence of an inflammatory component.
At 20 weeks, expression of RANKL and OPG in the tibia increased, while the increase in OPG occurred at earlier stages.
In VSMC, the addition of uremic serum and calcification medium increased calcium content and expression of RANKL and OPG. The addition of OPG and silencing of RANK inhibited this increase.
Conclusions: Our results confirm RANK/RANKL/OPG system involvement in the vascular calcification process.
Introduction: The most common cause of aortic stenosis is active calcium accumulation in the valve cusps, which implies serious clinical consequences. Various extracellular matrix metalloproteases (MMPs) have been implicated in the development of this disease. Therefore, the possible association between a functional MMP1 polymorphism and the amount of calcium deposited on the aortic valve is studied.
Patients and methods: 45 patients undergoing valve replacement were included in the study. The calcium content in valve cusps removed during surgery was determined by computed micro-tomography. DNA was extracted from peripheral blood samples for genotyping the -1607 1G>2G polymorphism of MMP1 by PCR and subsequent digestion.
Results: Significant differences were observed in the calcium content in aortic valves in individuals with different -1607 1G>2G genotypes (p=0.042). Thus, 2G allele carriers (homozygous or heterozygous) present higher calcium levels measured as BMD (p=0.004) as well as BV/TV (p=0.002). The association with BV/TV was independent of sex, age, degree of renal function and anatomy of the valve (p=0.02). BMD tendency (p=0.07) was also observed.
Conclusion: The association between 1G>2G MMP1 polymorphism and calcium content of the aortic valve suggests that the 1G allele would have a protective effect against calcium deposits. These results support the importance of further study to confirm whether this polymorphism could be used as a possible predictor of aortic stenosis development.
Sclerostin, encoded by the SOST gene, inhibits the Wnt pathway and, consequently, tends to decrease bone mass. Some polymorphisms of the SOST promoter have been associated with bone mineral density (BMD), but the molecular mechanisms involved are unknown. The aim of this study was to study the functional role of one polymorphism in vitro. We cloned the proximal promoter region of SOST gene, containing different alleles at the rs851054 SNP, in luciferase reporter vectors and transfected them into the cell lines HEK-293T, SAOS-2 and HOS-TE85. We did not find significant differences in the transcriptional activity of vectors with either the A or the G allele of the SNP. The co-transfection of vectors expressing RUNX2 and OSX markedly increased the transcriptional activity of the SOST promoter constructs (A allele, 2.5±0.9 fold, p<0.05; G allele, 1.9±0.8 fold, p<0.05), without significant differences between the rs851054 alleles. Moreover, no allele differences were detected in EMSAs. In conclusion, the DNA region upstream of the TSS of the SOST gene has a strong promoter activity that is enhanced by RUNX2 and OSX. Frequent allelic variants in this region have been associated with BMD, but the mechanisms involved remain to be elucidated because no functional differences between alleles were detected in vitro.read more
Prevalence of low levels of vitamin D in patients with breast cancer who live in Northern latitudes 21-22º
Objective: Vitamin D has been involved in various diseases, including cancer. Several studies have linked vitamin D levels with breast cancer. The aim of our study was to establish the importance of adequate vitamin D concentrations to prevent breast cancer.
Materials and methods: The study included 76 patients. Dietary habits, sun exposure, body mass index (BMI), and skin type were evaluated. Vitamin D determination in serum was measured by liquid chromatography. Vitamin D receptor pleomorphism was analyzed by immunohistochemistry.
Results: Vitamin D ingestion was deficient in 18 patients and 22 controls; and sufficient in 6 patients and 30 controls, odds ratio of 4.09, confidence interval 95% 1.04-11.0, (p=0.016). Sun exposure was present in 9 patients and 15 controls; 15 patients and 37 controls had less sun exposure or used protection. Two patients and 13 controls had normal levels of vitamin D (30-60), two patients and 26 controls had low levels (20-30), and 18 patients and 12 controls had very low levels (<20). Odds ratio for patients with vitamin D serum levels of 20 ng/mL or less, or higher was 9, CI 95% 2.95-27.5, (p<0.001). These levels were independent from BMI. Conclusion: Low concentrations of vitamin D are strongly related to breast cancer in a region with high solar exposure. More studies are needed to confirm this relationship.
Although most people’s osteoporotic conditions treated in clinical practice may be categorized in the postmenopausal osteoporosis group or related to aging, there are some osteoporosis cases linked to the development of some other disease or identifiable factor.
Most of these causes are associated with the taking of steroids, hypogonadism, malignant processes such as multiple myeloma, gastric surgery, alcoholism and treatment with anticonvulsant drugs. Hereditary hemochromatosis is another disorder related to the onset of osteoporosis. In this paper, we present 4 cases of patients with osteoporosis who also suffer hereditary hemochromatosis. The latter’s characteristics are described and also its possible relationship with bone disease.
Senile or involutional osteoporosis is a major problem in the developed world. Recent studies point to increased oxidative stress associated with aging, whether biological or chronological, as an important factor in its development. In this review paper, we focus on bone tissue disorders related to aging, the source of oxidative stress and negative influence on bone tissue. Finally, we consider the potential oxidative stress therapies currently being developed for this disease.read more