Bone Abstracts

Preclinical and epidemiologic data suggest that vitamin D deficiency may play a role in the pathogenesis and progression of prostate cancer. Based on recently reported genetic determinants of vitamin D insufficiency we investigated a functional T>G single nucleotide polymorphism (SNP) in the group-specific component (GC) gene for its association with 25-hydroxy (25-OH) vitamin D and 1.25 dihydroxy (1.25-OH) vitamin D levels and further to test a possible association with m...

Since the identification of LRP5 as the causative gene for the osteoporosis pseudoglioma syndrome (OPPG) as well as the high bone mass (HBM) phenotype, LRP5 and the Wnt/β-catenin signalling have been extensively studied for their role in the differentiation and proliferation of osteoblasts, in the apoptosis of osteoblasts and osteocytes and in the response of bone to mechanical loading. However, more recently the direct effect of LRP5 on osteoblasts and bone formation has...

The murine osteoprogenitor cell line, KS483 (Percuros, The Netherlands) is a well-established model for investigation of osteoblast differentiation and bone formation processes. The mesenchymal characteristics of this cell line allow it to differentiate into either adipocytes or mature, mineralizing osteoblasts. Various phases can be distinguished during osteoblast differentiation and maturation; namely proliferation, matrix formation, matrix maturation, and mineralization.</p...

Introduction: Paget’s disease of bone (PDB) has an autosomal-dominant mode of inheritance in one-third of cases. The germinal SQSTM1/P392L mutation is the most frequent mutation, present in 40% of patients with a familial form of PDB, and 8% of unrelated patients. Fibrous dysplasia (FD) is a rare bone disorder, mono or polyostotic, caused by post-zygotic mutations in GNAS gene, for which a PCR-clamping method was developed to ease their detection and avo...

Osteogenesis imperfecta is a clinically heterogeneous heritable connective tissue disorder. Most OI cases are due to mutations in type I collagen genes, COL1A1 and COL1A2 encoding the pro-alpha1(I) and pro-alpha2(I) chains respectively. However, genotype-phenotype correlation has not been completely elucidated yet. In this study we evaluated a familial case including a mother and a daughter, classified as OI type I. The daughter had more severe clinical featu...

Polynesians have higher bone mineral density and lower rate of hip fracture compared to age-matched Caucasian in New Zealand, and anecdotal evidence suggests that bones of Polynesian patients heal much faster than those of Caucasians. We compared gene expression in osteoblasts cultured form bone samples taken from patients of Polynesian and Caucasian origin, in order to identify genes and pathways that contribute to the greater density and accelerated healing of Polynesian bon...

The Runt-domain transcription factors Runx2 and Runx3 are known to drive chondrocyte maturation from prehypertrophic to the terminal stage. The RUNX family proteins form dimers with CBFb, and bind to consensus sequences of 5′-PuACCPuCa-3′ upstream of target genes to activate or repress transcription.To address the role of Runx3 transcription factor in zebrafish, we have isolated the different splice variants encoding distinct runx3 p...

Objective: The purpose of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in leptin (LEP), its receptor (LEPR) and β adrenergic receptor (ADRB) genes and bone mineral density (BMD) in postmenopausal Korean women.Methods: The LEP c.280G>A, LEPR c.326A>G, c.668A>G, c.1968G>C, c.2096C>T, ADRB2 c.46A>G, c.79C>G, c.718T>C, c....

Introduction: Aggressive periodontitis (AgP) is an inflammatory disease causing rapid loss of teeth in young patients.Aim: Determine degree of impact of COL1A1 gene on likelihood of AgP development.Materials and methods: Study included 47 patients with AgP, 40 patients with osteoporosis (OP), and 64 healthy patients (HP). Polymorphic variant c.104-441G>T (COL1A1) was studied. Statistics: Fisher’s...

It is well known that sex hormone deficiency leads to increased bone turnover and subsequent bone loss. The metabolism of estrogens involves, among others, oxidation (mainly hydroxylation) by CYPs. The aim of this study was to determine whether Leu432Val polymorphism in the CYP1B1 gene is present also in Slovak population and subsequently, if it is associated with femoral and spinal bone mineral density (FBMD and SBMD), bone remodeling markers and fracture incidence in this po...

The aims of this study were to establish the prevalence of the high bone mass (HBM) phenotype in a cohort of Spanish postmenapausal women (BARCOS); to determine whether any of the HBM cases carry LRP5 or DKK1 mutations; to test the hypothesis of an inverse correlation between the number of common variant risk alleles and HBM; and to characterize the expression of osteoblast-specific and Wnt pathway genes in primary osteoblast RNA samples from two HBM cases.</...

Over the past decade, many GWAs and meta-analyses were performed to identify genes and regions involved in bone metabolism and in the osteoporotic phenotypes. Nevertheless, the majority of these GWAS results were not tested at any functional level. This study aims to find and study functional regions in the RANK and RANKL genes that encode well-established proteins in the bone remodeling equilibrium. SNPs, chosen for their location in an evolutionary conserve...

Hip and forearm fractures are the two clinically most important non-vertebral fractures. Twin studies have demonstrated a high heritability of these fractures and the heritable component of fracture risk is largely independent of BMD.To identify common genetic variants associated with hip and forearm fractures, we performed a genome-wide association study (GWAS ~ 2.5 million SNPs) meta-analysis of two large fracture data sets within the well-characterize...

Introduction: Dentinogenesis imperfecta (DI) is a common dental aberration in patients with osteogenesis imperfecta (OI). Mutations that cause abnormal collagen chains will cause more serious types of OI and it has been claimed that DI should be a marker for qualitative defected collagen. It has also been supposed that normal development of teeth may be more dependent on normal α2(I) than normal α1(I) chains which are encoded by COLIA2 and COLIA1 ge...

Toll-like receptors (TLRs) appear to be involved in the pathogenesis of osteoarthritis (OA) and recent studies have suggested that polymorphisms in TLR9, an endosomal TLR are associated with knee OA in at least one population. TLR3 is also found on the surface of endosomes where they respond primarily to nucleic acid based pathogen-associated molecular patterns (PAMPs) from viruses and bacteria. We therefore determined the predictive value of TLR3 gene polymorphisms and furthe...

Heritability of bone mineral density (BMD) varies at skeletal sites, possibly reflecting different relative contributions of environmental and genetic influences. To quantify shared genetic influences across different sites, we estimated the genetic correlation of BMD at the upper limb (UL), lower limb (LL), and skull (S) obtained from whole body DXA scans, using bivariate genome-wide complex trait analysis (GCTA). The study (n=9395) combined data from the Avon Longit...

Introduction: The creatine kinase (CK) is a dimeric enzyme, involved in energetical metabolism. It is present in many tissues, but higher concentration in skeletal and cardiac muscle.Therefore, conditions that involve muscle tissue may increase this serum enzyme. Such enzyme elevation is usually observed in inflammatory myopathies and others autoimmune diseases.Sometimes some elevation in CK is not fully understood out off these co...