Bone Abstracts

Osteoporosis (OP) is characterised by reduced bone mass, due to an insufficient osteoblast-mediated bone formation, unable to replace the bone tissue removed by osteoclasts. Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into osteoblasts, adipocytes and chondrocytes. Epigenetic marks like DNA methylation could influence the differentiation potential of these cells into osteoblasts and, consequently, the risk of OP. To explore this hypothesis, we...

Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotype variability. The aim of this study was to identify osteoporosis-related SNPs by affecting the expression levels of mature microRNAs.The first approach was to perform an association analysis of putative functional SNPs located in pri-miRNA sequences of bone-related microRNAs with the lumbar spine and femoral neck (FN) bone mineral den...

Background: We previously reported that serum periostin levels are determined by additive genetic effects. Whether serum levels and/or SNPs in the periostin gene (Postn) contribute to bone microstructure however remains unknown.Aim: To investigate the association between periostin levels, Postn SNPs, bone-mass and bone microarchitecture in a cohort of postmenopausal women.Methods: A total of 648 postmenopausal women from the Geneva...

Background: Periostin is a matricellular protein involved in bone modeling and remodeling through the modulation of WNT-β catenin signaling in osteoblasts and osteocytes.Aim: To investigate the interaction between polymorphisms of six periostin SNPs and other gene polymorphism involved in periostin expression and activity on periostin serum levels and bone microarchitecture in a cohort of postmenopausal women.Methods: A total ...

Experimental studies suggested that both, oxidative stress and the Wnt pathway, are important factors in the regulation of bone remodeling. Thus, low antioxidant levels and elevated markers of Wnt pathway inhibitors (sclerostin) levels are associated with a reduced bone mineral density and increased risk of osteoporotic fracture. Whether oxidative stress and the Wnt pathway are related to fracture risk is poorly understood.M&M: Cross-sectional study ...

Purpose: Research suggests that dancers are at higher risk of developing low bone mineral density (BMD) compared with the general population. However, the associated factors contributing to low BMD in dancers are not fully understood. We aimed to assess the association of single-nucleotide polymorphisms (SNPs) in the Wnt/β-catenin and oestrogen receptor (ER) signalling pathways with low BMD in dancers.Methods: A genetic association study was conduct...

In a meta-analysis by Estrada et al. (2012), 56 loci were found associated with BMD, 14 of which were also associated with osteoporotic fracture. Several of these genes belong to the Wnt signaling pathway, including two inhibitors: DKK1 and SOST.To better understand the role of these genes in BMD determination and fracture susceptibility, we aimed to explore their allelic architecture by resequencing all coding exons and flanking region...

Introduction: Runt-related transcription factor 2 (RUNX2) is a major transcription factor essential for the regulation of osteoblast and chondrocyte differentiation, hence affecting skeletogenesis, bone and cartilage formation. The RUNX2 protein has unique consecutive polyglutamine and polyalanine repeats (Q/A) which are important for its transactivation function. Several variants within the RUNX2 gene have been implicated in osteoporosis and fracture susceptibility.<...

Vertebral fractures are the most common complication of osteoporosis, but little is known about the genetic determinants of susceptibility. Here we present the results of a genome wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with replication in 667 cases and 2105 controls. A locus tagged by a less frequent variant (rs10190845, A-allele MAF=0.05) was identified on chromosome 2q13 as a strong predictor of clinical verte...

Paget disease of bone (PDB) is a common metabolic bone disease characterized by increased bone resorption and disorganized bone formation which can affect single or multiple sites of bone. Although the exact cause of PDB is still controversial, genetic factor is considered to play an important role in PDB. The causative gene of classical PDB was identified as Q8STM1 gene. Familial expansile osteolysis caused by the mutation of TNFRSF11A(RANKL) gene a...

Introduction: Genetic disorders are usually characterised by subjective morphological traits. Mouse models should represent the human situation but it is difficult to translate morphology traits from one species to another. Thus, there is a demand to objectively assess morphological traits. Geometric morphometrics is a mathematical tool to evaluate morphology based on normalised three-dimensional coordinates. Here we use geometric morphometrics to compare the morphology of <em...

Acrofrontofacionasal Dysostosis type 1 (AFFND1) is a rare human syndrome (estimated prevalence lower than 1:1,000,000), characterized by bone abnormalities in addition to other multiple congenital anomalies and intellectual disability. Only four AFFND1 families, three of Brazilian and one of Indian origin, have been described so far and an autosomal recessive pattern of inheritance has been suggested. The patients are severely affected: the main clinical features are intellect...

Circulating microRNAs (miRNAs) are currently being investigated as novel biomarkers for osteoporosis and osteoporotic fractures. The aim of the present study was to investigate the differential expression of specific circulating micro RNAs known to regulate bone metabolism and homeostasis in postmenopausal osteoporotic women with and without vertebral fractures. For the analysis, miRNAs were isolated from the serum of 24 osteoporotic patients with at least one moderate vertebr...

Skeletal strength, maintained through bone remodelling, is regulated through complex communication networks between bone cells and other tissues including endocrine cells. Bone also functions as an endocrine organ in its own right. The peptide hormone amylin (or Islet Amyloid Polypeptide (IAPP)), has links to both bone and energy metabolism. A member of the calcitonin family of peptides, it is co-secreted with insulin from pancreatic β-cells and is linked with diabetes-as...

The R-spondins are a family of four small, secreted agonists of the Wnt signaling pathway. Growing evidence from both in vitro studies and in vivo models supports the major role of these proteins in the skeletal development processes. In humans, common genetic variation in the RSPO3 gene has been associated with BMD in large scale GWAS study.This study aimed at further investigation of the genetic and functional contributions of the R-s...

miRNAs are epigenetic regulators of gene expression, increasingly recognised as prominent regulators of bone metabolism. Following our in vitro studies of miRNAs profiles in osteoblasts we extended the research to human bone samples. Our aim was to find and functionally validate miRNAs differentially expressed in osteoporotic and osteoarthrotic bone with potential for targeting genes relevant in bone metabolism.Trabecular bone tissue samples wer...

Molecularly characterized epigenetic networks that control bone formation and are altered during aging are necessary to uncover new potential targets for osteoanabolic therapy. Our contribution to the iBONE consortium is to identify osteoanabolic epigenomic regulators by screening which are involved in osteoblast phenotype and differentiation. This study will be done by a 3 step approach including: siRNA screening for epigenomic regulators of osteoblastic differentiation and v...

Background: Advancing maternal age at childbirth has been associated with a higher risk of pregnancy complications and with adverse short-term and long-term offspring health outcomes, but little is known about the effects of increasing maternal age on offspring bone acquisition.Objective: To investigate associations of maternal age at childbirth with offspring bone parameters in healthy men at the age of peak bone mass.Methods: We ...

Increasing bone formation is an effective approach to prevent osteoporotic fractures. Although the intermittent administration of PTH is an established osteoanabolic therapy and an anti-Sclerostin antibody (Scle-AB) is currently being tested in phase 3 clinical trials, a great need exists for additional bone anabolic agents. Thus, in the context of a bi-national consortium we aim to uncover novel epigenomic networks controlling bone formation to identify new epigenomic approac...

Introduction: Mitochondrial dysfunction is associated with several clinical outcomes including diabetes and myopathy and is implicated in the human aging process. We previously showed that the mitochondrial DNA point mutation mtDNA3243A>G is associated with lower BMD and altered bone structure. The aim of this study was to assess bone turnover markers in individuals with the mutation and controls.Methods: We recruited 45 patients (29 female, 16 male)...

During aging bone resorption often increases while bone formation decreases, thereby reducing bone mass and bone mineral density (BMD) and leading to osteoporosis. Evidence suggests that extrinsic factors may influence bone remodeling. While poorly understood, these mechanisms may function by inducing epigenomic programs that diminish the bone forming capacity of osteoblasts. This study is part of a bi-national consortium aimed at uncovering epigenomic networks controlling the...

Osteoarthritis is a complex pathogenesis because diverse factors interact causing a process of deterioration of the cartilage and the subchondral bone. Despite the multifactorial nature of the knee osteoarthritis, it is related to a strong genetic component. Determination of molecular genetic causes of osteoarthritis is an actual problem. There are several approaches to assess the contribution of a candidate gene in the pathogenesis of osteoarthritis. The aim of the study was ...

Osteoporosis has a complex etiology and is considered a multifactorial polygenic disease in which genetic determinants are modulated by hormonal, environmental, and nutritional factors.Polymorphism of the vitamin D receptor gene has been reported to play a major role in variations for genetic regulation of bone mass but its role within various ethnic populations is not clear. Estrogens are known to play an important role in regulating bone homeostasis, t...

OPTN seems to have an important role in bone metabolism by being part of NfkB pathway. CCDC3 is highly expressed in adipocytes and it seems to be negatively regulated by TNFa, however the mechanisms are not very clear. These genes have a ‘head-to-head’ orientation in the genome, which suggests that they might be regulated by a bidirectional promoter that coordinates the expression of both genes in different tissues. Using bioinformatic tools we analyzed the shared re...

Optineurin (OPTN) is a protein encoded by the OPTN gene. This protein is involved in several cellular mechanisms such as autophagy, NF-κB signaling, cellular morphogenesis, membrane and vesicle trafficking, and transcription activation. Mutations in OPTN have been described in glaucoma, amyotrophic lateral sclerosis and other neurological diseases. More recently, a polymorphism in this gene was also identified by a genome wide association study to be ass...