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New insights into the regulation of cathepsin K gene expression by osteoprotegerin ligand.

Cathepsin K plays a key role in bone resorption. We provide the first evidence that osteoprotegerin ligand (OPGL), a critical pro-resorptive cytokine, acutely stimulates the expression of cathepsin K in osteoclasts. We used in situ RT-PCR and real time quantitative RT-PCR to analyze cathepsin K gene expression. OPGL enhanced cathepsin K mRNA levels in mature osteoclasts isolated from rat neonatal long bones. OPGL together with macrophage colony-stimulating factor (M-CSF) also stimulated cathepsin K gene expression in monocytic cells and multinucleate osteoclasts in bone marrow cultures. Real t

Cloning, sequencing, and functional characterization of the vitamin D receptor in vitamin D-resistant New World primates.

New World primates (NWPs) have high circulating 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels. Comparable levels would be harmful to Old World primates (OWPs) and humans. Thus, NWPs must have developed mechanisms of 1,25-(OH)2D resistance to survive. In humans, patients with hypocalcemic vitamin D-resistant rickets type II have high circulating vitamin D levels and vitamin D resistance due to expression of a dysfunctional vitamin D receptor (VDR). To examine if this could wholly or in part explain vitamin D resistance in NWPs, VDR from Saguinus oedipus (cotton top tamarin) NWP B95-8 cells was c

Role of the hypoxia sensing system, acidity and reproductive hormones in the variability of vascular endothelial growth factor induction in human breast carcinoma cell lines.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor implicated in many pathological processes. We investigated the regulation of 4 alternatively spliced isoforms (121, 165, 189 and 206 amino acids) by hypoxia, hypoglycemia, acidity, female reproductive hormones and vitamin D in breast carcinoma cell lines representing different tumor phenotypes. There was a 17-fold difference in total VEGF mRNA expression across the cell lines. The isoform expression, 121 > 165 > 189, was unchanged by different culture conditions. Hypoxia was the most potent stimulus, and the cell lines dem

Hypophosphatemia in cancer patients.

Dysregulation of phosphorus homeostasis resulting in hypophosphatemia is common in cancer patients and can result in serious complications and impact outcomes. Several factors, including critical illness, nutritional status, cancer type and therapy, influence the development of hypophosphatemia. Hypophosphatemia can develop as a result of phosphaturic mesenchymal tumors or as a paraneoplastic phenomenon. The clinical presentation for hypophosphatemia varies depending on the duration and severity of the hypophosphatemia and affects several organ systems. Among other serious effects, hypophospha

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… Its expression is upregulated by low dietary phosphate [ 27 ] and calcitriol [ 28 ] and inhibited by niacin. PTH increases intestinal absorption of phosphate indirectly by increasing the production of calcitriol in the kidneys. … In patients with nonresectable FGF-23-secreting tumors, medical management consists of dietary phosphate and calcitriol supplementation. …

Genetic variants in vitamin D metabolism-related genes are associated with vitamin D status and adiposity markers.

Single nucleotide variants (SNVs) in vitamin D (VD) metabolism genes have been shown to be associated with serum 25(OH)D concentrations. Although these associations have been reported in other populations, they are less studied in Mexico, a country with high vitamin D deficiency (VDD) despite ample sun exposure. Therefore, we investigate the association between VD-metabolism related SNVs, serum 25(OH)D concentrations, and their impact on VDD and adiposity indicators. We hypothesized that SNVs are associated with serum 25(OH)D concentrations in the Mexican population. We included 1977 individua

Molecular study of vitamin D metabolism-related single nucleotide polymorphisms in cardiovascular risk: a case-control study.

Cardiovascular diseases (CVDs) constitute a major global health problem, being the leading cause of death. Several risk factors for CVDs have been identified, including tobacco use, unhealthy diet, and physical inactivity. However, the role of genetic factors in CVDs remains unclear. Recent studies suggest that vitamin D deficiency is associated with an increased risk of CVDs. Therefore, the aim of this study is to assess the impact of 13 single nucleotide polymorphisms (SNPs) located in genes involved in vitamin D metabolism (VDR, GC, CYP27B1, CYP2R1, and CYP24A1) on the risk of developing CV

Oncomir MicroRNA-346 Is Upregulated in Colons of Patients With Primary Sclerosing Cholangitis.

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder that is frequently associated with ulcerative colitis (UC). Patients with PSC and UC (PSC-UC) have a higher risk of colorectal neoplasia compared with patients with UC. The oncogenic properties of microRNA-346 (miR-346) have been recently reported. We investigated the expression of miR-346 and its 2 target genes, the receptor of vitamin D (VDR), and the tumor necrosis factor-α (TNF-α), which are known to modulate carcinogenesis. METHODS: Ascending and sigmoid colon biopsies were obtained from patients with PSC,

Calcium-Sensing Receptor Genotype and Response to Cinacalcet in Patients Undergoing Hemodialysis.

BACKGROUND AND OBJECTIVES: We tested the hypothesis that single nucleotide polymorphisms (SNPs) in the calcium-sensing receptor (CASR) alter the response to the calcimimetic cinacalcet. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed DNA samples in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial, a randomized trial comparing cinacalcet to placebo on a background of usual care. Of the 3883 patients randomized, 1919 (49%) consented to DNA collection, and samples from 1852 participants were genotyped for 18 CASR polymorphisms. The European ancest

Bsm1 vitamin D receptor polymorphism and calcium homeostasis following bariatric surgery.

PURPOSE/AIM: To evaluate the association between the Bsm1 vitamin D receptor polymorphism and the calcium-vitamin D-parathormone axis following bariatric surgery. MATERIALS AND METHODS: This cross-sectional study included 86 morbidly obese patients, who underwent either gastric bypass or sleeve gastrectomy, with a mean follow-up of four years. Calcium metabolism indices and bone turnover markers were assessed according to the presence of secondary hyperparathyroidism and the Bsm1 vitamin D receptor genotypes. RESULTS: Secondary hyperparathyroidism (42.2% of sample) was associated with lower

Tumor-produced versican V1 enhances hCAP18/LL-37 expression in macrophages through activation of TLR2 and vitamin D3 signaling to promote ovarian cancer progression in vitro.

Tumor-associated macrophages have been shown to promote tumor growth. They may have an obligatory function in angiogenesis, invasion, and metastasis through release of inflammatory mediators. Their presence in ovarian cancer has been correlated with poor prognosis in these patients. The human cationic antimicrobial protein-18 (hCAP18)/LL-37 was originally identified as an effector molecule of the innate immune system. It is released by innate immune cells, such as macrophages, to combat microorganisms. Previous studies have characterized the hCAP18/LL-37 as a growth factor that has been shown

Abnormal XPD-induced nuclear receptor transactivation in DNA repair disorders: trichothiodystrophy and xeroderma pigmentosum.

XPD (ERCC2) is a DNA helicase involved in nucleotide excision repair and in transcription as a structural bridge tying the transcription factor IIH (TFIIH) core with the cdk-activating kinase complex, which phosphorylates nuclear receptors. Mutations in XPD are associated with several different phenotypes, including trichothiodystrophy (TTD), with sulfur-deficient brittle hair, bone defects, and developmental abnormalities without skin cancer, xeroderma pigmentosum (XP), with pigmentary abnormalities and increased skin cancer, or XP/TTD with combined features, including skin cancer. We describ

Alternative promoters and renal cell-specific regulation of the mouse type IIa sodium-dependent phosphate cotransporter gene.

The type IIa sodium-dependent phosphate cotransporter (NPT2a) expressed in renal proximal tubules represents an important determinant in maintaining inorganic phosphate (Pi) homeostasis. In the present study, we identified two variant transcripts of the mouse NPT2a gene, Npt2a-v1 and Npt2a-v2, characterized by the presence of alternative first exons (either exon 1A or exon 1B). The chromosomal structure analysis revealed that the Npt2a gene comprises of two promoters (promoters 1 and 2) and 14 exons, and spans approximately 17 kb. Quantitative PCR analysis showed that renal mRNA levels of both

Determinants of bone mineral density and spinal fracture risk in postmenopausal Japanese women.

The present study analyzed the factors that determine bone mineral density (BMD) and predict spinal fracture risk in postmenopausal Japanese women. Two hundred and five postmenopausal Japanese women aged 48-84 years (mean age 64 years) were enrolled in the cross-sectional study. BMD of the lumbar spine, femoral neck and total body as well as body composition were measured by dual-energy X-ray absorptiometry (DXA). Mid-radial BMD was measured by single-photon absorptiometry. We also determined serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-2, -3 and osteocalcin as well

Hypercalcemia of Malignancy and Medication-Related Osteonecrosis of the Jaw Following Denosumab Discontinuation in Metastatic Breast Cancer: A Case Report.

Hypercalcemia of malignancy (HCM) is a common and serious complication in patients with advanced cancer and is associated with significant morbidity and mortality. Standard long-term management of HCM relies on anti-resorptive therapies such as bisphosphonates and denosumab, both of which act by inhibiting osteoclast-mediated bone resorption but carry the risk of medication-related osteonecrosis of the jaw (MRONJ). This case illustrates a patient with metastatic breast cancer (MBC) who developed recurrent, severe hypercalcemia after discontinuing denosumab due to MRONJ, followed by profound hy

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… In light of her persistently suppressed PTH and the non-endocrine mechanism underlying her hypercalcemia, both calcium supplements and calcitriol remained discontinued. … She was discharged on vitamin D3 1,000 IU daily and calcitonin nasal spray (200 units/actuation), discontinuing calcitriol. The patient was admitted on June 6, 2025, with symptoms of lip tingling and numbness in her fingers. …

Vitamin D, vitamin D binding protein, vitamin D receptor levels and cardiac dysautonomia in patients with multiple sclerosis: a cross-sectional study.

OBJECTIVES: Vitamin D is a pleiotropic steroid hormone that modulates the autonomic balance. Its deficiency has been described as an environmental risk factor for multiple sclerosis (MS). The aim of this study was to investigate the serum levels of vitamin D, vitamin D binding protein (VDBP) and vitamin D receptors (VDR) and to evaluate cardiac dysautonomia in MS patients due to bidirectional interaction between vitamin D and the autonomic nervous system. METHODS: The current cross-sectional study was conducted on 26 patients with relapsing-remitting MS and on 24 healthy controls. Twenty-four

Epidermolysis bullosa: Advances in research and treatment.

Epidermolysis bullosa (EB) is the umbrella term for a group of rare inherited skin fragility disorders caused by mutations in at least 20 different genes. There is no cure for any of the subtypes of EB resulting from different mutations, and current therapy only focuses on the management of wounds and pain. Novel effective therapeutic approaches are therefore urgently required. Strategies include gene-, protein- and cell-based therapies. This review discusses molecular procedures currently under investigation at the EB House Austria, a designated Centre of Expertise implemented in the European

Oleanolic Acid Exerts Osteoprotective Effects and Modulates Vitamin D Metabolism.

Oleanolic acid (OA) is a triterpenoid with reported bone anti-resorption activities. The present study aimed to characterize its bone protective effects in vivo and to study its effects on vitamin D metabolism, both in vivo and in vitro. OA significantly increased bone mineral density, improved micro-architectural properties, reduced urinary Ca excretion, increased 1,25(OH)₂D₃ and renal CYP27B1 mRNA expression in mature C57BL/6 ovariectomised (OVX) mice. OA also improved bone properties, Ca balance, and exerted modulatory effects on renal CYP27B1 and CYP24A1 expressions in aged normal female S

1,25-Dihydroxyvitamin-D3 prevents the development of diabetic cardiomyopathy in type 1 diabetic rats by enhancing autophagy via inhibiting the β-catenin/TCF4/GSK-3β/mTOR pathway.

Diabetic cardiomyopathy (DCM) can increase the risk of heart failure and death in diabetic patients. However, no effective approaches are available to prevent its progression and development. Studies have shown that vitamin D is greatly implicated in cardiac hypertrophy and fibrosis, and there is a high prevalence of vitamin D deficiency in diabetic patients. In this study, we investigated whether 1,25-Dihydroxyvitamin-D3 (1,25D3) can improve DCM through a vitamin D receptor (VDR)-dependent mechanism associated with autophagy and the β-catenin/T-cell factor/lymphoid enhancer factor (TCF4)/glyc

A statistical analysis plan for the efficiency and safety of Chinese herbal medicine used concurrently with topical therapy for psoriasis vulgaris.

BACKGROUND: Psoriasis vulgaris (PV) has been causing increasing concern due to its highly prevalent, harmful and therapy-resistant characteristics. The YXBCM01 (Chinese herbal medicine) for PV trial evaluates the effects of YXBCM01 on relapse rate in patients suffering from PV. As an update to the published design and method for the trial, this paper presents the statistical plan for the main publication to avoid the risk of outcome reporting bias, selective reporting, and data-driven results. METHODS/DESIGN: This trial is a multicenter, randomized, double-blind, placebo-controlled, parallel-

Integrative role of vitamin D related and Interleukin-28B genes polymorphism in predicting treatment outcomes of Chronic Hepatitis C.

BACKGROUND: Improving prediction of treatment outcomes in chronic hepatitis C (CHC) genotype 4 (G4) is necessary to increase sustained viral response (SVR) rates. Vitamin D related and interferon stimulated genes are good candidates as they are recently crosstalk altering interferon response. Thus single nucleotide polymorphisms (SNPs) within some of these genes and multiple stepwise regression analysis including other independent predictors (IL28B(rs12979860), serum 25OH-vitamin D, serum alfa-fetoprotein (AFP)) were performed on a cohort of 200 Egyptian CHC patients treated with Pegylated int