MiR-148a the epigenetic regulator of bone homeostasis is increased in plasma of osteoporotic postmenopausal women.

Background: Osteoporosis is a prevalent skeletal disorder characterized by reduced bone mineral density and microarchitectural deterioration of bone tissue, resulting in bone fragility and low-trauma fractures. Imaging techniques are routinely used to detect low bone mass; however, they are unable to identify deterioration of bone quality. Recently, microRNAs have emerged as regulators of bone remodelling and potentially also as a new class of sensitive biomarkers of bone health to aid in diagnosis and treatment monitoring of osteoporosis.

ADRA2A is involved in neuro-endocrine regulation of bone resorption.

Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through β2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of α2A-AR in bone. The aim of this study was to investigate the presence of α2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans.

Raloxifene pharmacodynamics is influenced by genetic variants in the RANKL/RANK/OPG system and in the Wnt signaling pathway.

Background: Raloxifene is a selective estrogen receptor (ER) modulator (SERM) used for the treatment of osteoporosis. However, its efficacy and also its safety vary greatly among treated patients, and it might be influenced by the individuals' genetic background. As the receptor activator of the nuclear factor κB (RANK) ligand (RANKL)/RANK/osteoprotegerin (OPG) system is essential for osteoclastogensis and Wnt signaling pathway for osteoblastogenesis, we decided to evaluate the raloxifene treatment in regard to selected polymorphisms in key genes of these two main bone regulatory pathways.

Interleukin-1α gene variants influence bone mineral density and the risk of osteoporotic hip fractures in elderly Slovenian people.

Background: Osteoporosis is a skeletal disorder, characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to increased risk of fracture. Recently, the role of age-related pro-inflammatory cytokines, such as interleukin (IL)-1α, in stimulating bone resorption has been suggested. As osteoporosis has a strong genetic background, the aim of our study was to evaluate the association of two IL-1α gene single nucleotide polymorphisms (SNPs) rs2071375 (+12534G>A) and rs17651 (+4845G>T) with osteoporotic phenotypes as well as to find the association with IL-1α gene expression in human bone tissue.

Assessment of gene-by-sex interaction effect on bone mineral density.

Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts.

BMD values and GSTM3 gene polymorphisms in combination with GSTT1/GSTM1 genes: a genetic association study in Slovenian elderly.

Background: Much research suggests that oxidative stress is associated with osteoporosis development. Glutathione S-transferases mu3 (GSTM3) are an important group of detoxifying enzymes that eliminate oxidative stress-related products.

Objectives: To examine the associations of functional GSTM3 gene polymorphisms (Val224Ile and insdelAGG), their haplotypes and, in combination with GSTT1-null and GSTM1-null polymorphisms, with bone mineral density (BMD) measured at femoral neck (_fn), lumbar spine (_ls) and total hip (_th) and biochemical bone turnover markers in 593 Slovenian elderly women and 119 Slovenian elderly men.

Testing GSTP1 genotypes and haplotypes interactions in Slovenian post-/pre-menopausal women: novel involvement of glutathione S-transferases in bone remodeling process.

Objectives: Osteoporosis (OP) is an age-related disease associated with increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense system, such as low activity of glutathione S-transferase (GST) family. The enzyme activity of the member of GSTs, GSTP1, depends on gene polymorphisms such as: Ala114Val and Ile105Val. The aim of this study was to evaluate the association between genetic polymorphisms of the GSTP1 gene and BMD variation and biochemical bone remodeling markers in 523 Slovenian pre- and post-menopausal women.

Antioxidant enzymes GSR, SOD1, SOD2, and CAT gene variants and bone mineral density values in postmenopausal women: a genetic association analysis.

Objective: Oxidative stress participates in decreasing bone formation and stimulating bone resorption. Furthermore, antioxidant enzymes have been observed to have low protective activity in women with osteoporosis.The aim of the present study was to examine any association of selected gene polymorphisms of the glutathione S-reductase (GSR), superoxide dismutase (SOD1 and SOD2), and catalase (CAT) genes, alone or in combination, with the bone mineral density (BMD) values of femoral neck (fn), lumbar spine (ls), and total hip (th) in Slovenian postmenopausal women.

Opposite effects of GSTM1--and GSTT1: gene deletion variants on bone mineral density.

Oxidative stress is associated with osteoporosis. The glutathione S-transferases form the major detoxifying group of enzymes responsible for eliminating products of oxidative stress. We have therefore proposed GSTM1 and GSTT1 genes as candidates for studying the genetics of osteoporosis.

PPARG gene promoter polymorphism is associated with non-traumatic hip fracture risk in the elderly Slovenian population: a pilot study.

Objectives: Peroxisome proliferator-activated receptor γ (PPARγ), an essential transcription factor for adipogenesis, has been implicated in pathogenesis of osteoporosis. The association of three single nucleotide polymorphisms in the PPARG gene with hip fracture risk, bone mineral density (BMD) and biochemical markers of bone turnover was investigated in the elderly.

Design And Methods: Six hundred sixty-seven elderly Slovenians were genotyped for SNPs rs12497191, rs1801282 and rs3856806.

TNFRSF11B gene polymorphisms 1181G > C and 245T > G as well as haplotype CT influence bone mineral density in postmenopausal women.

Objectives: Osteoprotegerin (OPG) inhibits osteoclast function by acting as a decoy receptor for receptor activator of nuclear factor-κB ligand (RANKL), thus being an important candidate gene for osteoporosis. Three recent genome-wide association studies also identified the TNFRSF11B gene, coding for OPG, as playing a key role in bone mineral density (BMD) regulation. As variations in the TNFRSF11B gene could alter the susceptibility to osteoporosis, the aim of study was to investigate association of two TNFRSF11B gene polymorphisms with BMD and serum OPG concentration in postmenopausal women.

-1227C>T polymorphism in the pleiotrophin gene promoter influences bone mineral density in postmenopausal women.

Our gene expression microarray data of primary cultures of osteoblasts revealed that the expression of the pleiotrophin (PTN) gene is decreased in osteoporosis. PTN is involved in osteoblasts' proliferation and differentiation, response to mechanical stimuli and cross-talk with Wnt signaling. On the basis of these findings, we studied the PTN gene as a candidate gene for genetic susceptibility to osteoporosis.

Influence of spironolactone treatment on endothelial function in non-obese women with polycystic ovary syndrome.

Objective: Accumulating evidence connects polycystic ovary syndrome (PCOS) with increased risk of cardiovascular disease. Endothelial dysfunction is present in PCOS and represents an early, reversible marker of cardiovascular damage. As androgens and renin-angiotensin-aldosterone system are implicated in the atherogenesis process of PCOS, we tested the hypothesis that treatment with spironolactone, an androgen and mineralocorticoid receptor blocking drug, might reverse endothelial dysfunction in PCOS.

Association between adiponectin and low-grade albuminuria is BMI-dependent in type 2 diabetes.

Aim: Low-grade albuminuria is a marker of increased risk for both cardiovascular and renal disease. Adiponectin, with its insulin-sensitizing, anti-inflammatory and antiatherogenic properties, is associated with cardiovascular as well as renal disease. Limited and conflicting data exist on the association of adiponectin with low-grade albuminuria.

The antioxidant enzyme GPX1 gene polymorphisms are associated with low BMD and increased bone turnover markers.

Recently, oxidative stress has been suggested as participating in the development of osteoporosis. Glutathione peroxidase 1 (GPX1) is one of antioxidant enzymes responsible for the defence of cells against oxidative damage and thus for protection against age related diseases such as osteoporosis. The aim of present study was to associate genetic variances of GPX1 enzyme with bone mineral density (BMD) and biochemical bone turnover markers and to show the influence of antioxidative defence system in genetics of osteoporosis.

XbaI polymorphism of the estrogen receptor alpha gene influences the effect of raloxifene on the endothelial function.

Objectives: Cardiovascular disease is the leading cause of death in postmenopausal women and estrogen deficiency may be an important factor in its development. The selective estrogen receptor modulator, raloxifene, exerts a part of its actions through the estrogen receptor alpha (ESR1) activation. We explored if polymorphisms of the ESR1 modify the effects of 6 months raloxifene treatment on endothelial function.

Analysis of association of LRP5, LRP6, SOST, DKK1, and CTNNB1 genes with bone mineral density in a Slovenian population.

The Wnt pathway has a bifunctional role in bone mass regulation, influencing osteoblasts and osteoclasts. The Wnt pathway genes are therefore candidate genes for susceptibility to osteoporosis. In our study, we focused on the effects of polymorphisms in selected Wnt pathway genes: low-density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6), Dickkopf1 (DKK1), sclerostin (SOST), and beta-catenin (CTNNB1).

Gene-gene interactions in RANK/RANKL/OPG system influence bone mineral density in postmenopausal women.

Receptor activator of nuclear factor kappaB (RANK) is one of the proteins in regulation of osteoclastogenesis via RANK/RANKL/OPG. Gene that codes for RANK protein (TNFRSF11A) was associated with osteoporotic fractures in a recent genome-wide association study. As variations in the RANK gene could alter its expression and activity, the aim of our study was to evaluate the influence of four RANK gene polymorphisms on bone mineral density (BMD) and biochemical markers.

A microarray based identification of osteoporosis-related genes in primary culture of human osteoblasts.

Genetic factors influencing the pathogenesis of osteoporosis are still largely unknown. We employed genome-wide gene expression approach in order to discover novel genes involved in the pathogenesis of osteoporosis. To this end, primary cultures of osteoblasts isolated from osteoporotic and non-osteoporotic human bone tissue samples were prepared.

Adipocytokines are associated with renal function in patients with normal range glomerular filtration rate and type 2 diabetes.

Introduction: Adipocytokines represent a molecular link between metabolic factors and vascular function. The purpose of our study was to investigate the relationship between adiponectin, leptin and renal function parameters in patients with glomerular filtration rate (GFR) above 90 ml/min/m(2) and type 2 diabetes.

Materials And Methods: In 52 patients, plasma (P-) and urinary (U-) adiponectin and leptin were determined by radioimmunoassay and ELISA, respectively.

The combinations of polymorphisms in vitamin D receptor, osteoprotegerin and tumour necrosis factor superfamily member 11 genes are associated with bone mineral density.

1alpha,25-dihydroxyvitamin D(3) upregulates tumour necrosis factor superfamily member 11 (TNFSF11) that codes for the receptor activator of nuclear factor kappaB ligand (RANKL), and downregulates osteoprotegerin (OPG) expression. We have analyzed the individual effects of polymorphisms in the vitamin D receptor gene (VDR), OPG and TNFSF11, and searched for interactions between them. Six hundred and forty one subjects were evaluated: 239 osteoporotic and 228 non-osteoporotic post-menopausal, 57 pre-menopausal women and 117 elderly men.

Improvement of endothelial function with metformin and rosiglitazone treatment in women with polycystic ovary syndrome.

Objective: There is evidence of preclinical cardiovascular disease even in young women with polycystic ovary syndrome (PCOS). The aim of our study was to assess and compare the effects of metformin (MET) and rosiglitazone (ROSI) on endothelial function in PCOS patients.

Methods: For 6 months, 26 women with PCOS received either MET or ROSI.

Assessment of insulin resistance in young women with polycystic ovary syndrome.

Objectives: To determine whether serum levels of potential markers could detect insulin resistance (IR) in young women with polycystic ovary syndrome (PCOS).

Methods: Serum levels of fasting glucose, insulin, intact proinsulin, resistin, and adiponectin were measured in 50 women with PCOS and known homeostatic model assessment (HOMA)-IR values (>or=2 indicating IR). The women were all younger than 25 years.

Tumour necrosis factor superfamily member 11 gene promoter polymorphisms modulate promoter activity and influence bone mineral density in postmenopausal women with osteoporosis.

Tumour necrosis factor superfamily member 11 (TNFSF11) gene, that codes for receptor activator of nuclear factor-kappaB ligand, is one of the candidate genes for the genetic susceptibility to osteoporosis. As variations in the TNFSF11 gene promoter could alter its expression, the aim of the study was to evaluate the functional influence of three polymorphisms in the promoter and to investigate their association with bone mineral density (BMD) and biochemical markers in postmenopausal women. A total of 404 postmenopausal women were genotyped for the presence of TNFSF11 gene promoter polymorphisms -290C>T, -643C>T and -693G>C.