Bone Abstracts

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...

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...

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...

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...

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...