Searchable abstracts of presentations at key conferences on calcified tissues

ba0001pp273 | Genetics | ECTS2013

Functional analysis of the two Runx3 promoters in osseous and non-osseous cells: implications for tissue/differentiation specific transcription of distinct isoforms

Conceicao Natercia , Simoes Brigite , Cancela M Leonor

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...

ba0001pp481 | Other diseases of bone and mineral metabolism | ECTS2013

Single nucleotide polymorphisms identification and functional analysis in PDB6 locus: a target locus for Paget's disease of bone

Silva Iris , Conceicao Natercia , Michou Laetitia , Cancela M Leonor

Introduction: The etiology of Paget’s disease of bone (PDB) is not fully understood, but genetic factors play a clearly important role. Single nucleotide polymorphisms (SNPs) of OPTN gene within PDB6 locus have been highly associated with PDB, but no PDB causal mutation or functional effect on PDB development were reported to date. We aimed to identify functional SNPs associated with this bone disease.Methods: Relevant candidate genes from PDB6 locu...

ba0003pp191 | Genetics | ECTS2014

Functional analysis of a promoter polymorphism of optineurin, a gene associated to Paget's disease of bone

Silva Iris , Conceicao Natercia , Michou Laetitia , Cancela Leonor

Paget’s disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. Optineurin (OPTN) gene, which is located within the PDB6 locus, and appears to be upregulated by TNFα and NF-kB, has been found to be associated with PDB in several European populations with PDB in genome-wide association studies. Several nucleotidic variations in OPTN were previously associated with PDB and may contribute to PDB pathogenesis. Recently, we have identi...

ba0005p256 | Genetics and Epigenetics | ECTS2016

OPTN and CCDC3 share a bidirectional promoter region that is regulated by NfkB

Silva Iris A.L. , Conceicao Natercia , Leonor Cancela M.

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...

ba0005p257 | Genetics and Epigenetics | ECTS2016

Comparative analysis of human and zebrafish OPTN: molecular and evolutionary perspectives

Silva Iris A.L. , Conceicao Natercia , Michou Laetitia , Leonor Cancela M.

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...

ba0005p221a | Chondrocytes and cartilage | ECTS2016

miR-214: a novel regulator of chondrogenesis?

Roberto Vania P , Conceicao Natercia , Nunes Maria J , Rodrigues Elsa , Cancela M Leonor , Tiago Daniel M

Skeletogenesis is an intricate process controlled by numerous transcriptional factors, hormones and signalling pathways. Recently, microRNAs emerged as important players in skeletogenesis but, only few were identified and most of their targets remain unknown. Previous works showed that miR-199a-2/214 cluster is essential for skeletal development and that miR-214 inhibits bone formation in mammals. However, data regarding its skeletal role in other vertebrates is scarce and its...