miR profile in pagetic osteoclasts: from large-scale sequencing to gene expression study

Background: Paget's Disease of Bone (PDB) is characterized by excessive and disorganized bone remodeling, in which bone-resorbing osteoclasts play a key role. Strong genetic components and environmental factors contribute to the etiopathogenesis of PDB. We hypothesized that dysregulated microRNA (miR) expression contributed to the osteoclast phenotype in PDB. Results: From deep sequencing, six mature miRs, miR-29b1-3p, miR-15b-5p, miR-181a-5p, let7i-3p, miR-500b-5p, and miR-1246, were found to be significantly decreased in overactive osteoclasts from the PDB patients compared to those in the healthy controls. The differential expression of the miRs was confirmed by the analysis of a larger independent cohort using qPCR. Conclusion: We identified six miRNAs whose expression were deregulated in PDB condition. Many of these miRs are known to modulate many critical aspects of osteoclast generation and function by coordinating their regulation of gene expression. Our results enhance the understanding of osteoclast biology in PDB disease Blood samples were obtained from 9 patients with PDB and 9 sex- and age- matched controls. Peripheral blood mononuclear cells (PBMCs) were differentiated into osteoclasts in 3-week in-vitro cultures and osteoclast samples were sent to be sequenced using multiplex sequencing on a HiSeq (Illumina) instrument (Genome Quebec).