Systematic identification, characterization and target gene analysis of microRNAs involved in osteoarthritis subchondral bone pathogenesis

Prasadam, Indira, Batra, Jyotsna, Perry, Samuel, Gu, Wenyi, Crawford, Ross and Xiao, Yin (2016) Systematic identification, characterization and target gene analysis of microRNAs involved in osteoarthritis subchondral bone pathogenesis. Calcified Tissue International, 99 1: 43-55. doi:10.1007/s00223-016-0125-7


Author Prasadam, Indira
Batra, Jyotsna
Perry, Samuel
Gu, Wenyi
Crawford, Ross
Xiao, Yin
Title Systematic identification, characterization and target gene analysis of microRNAs involved in osteoarthritis subchondral bone pathogenesis
Journal name Calcified Tissue International   Check publisher's open access policy
ISSN 1432-0827
0171-967X
Publication date 2016-07
Year available 2016
Sub-type Article (original research)
DOI 10.1007/s00223-016-0125-7
Open Access Status Not Open Access
Volume 99
Issue 1
Start page 43
End page 55
Total pages 13
Place of publication New York, NY, United States
Publisher Springer New York LLC
Collection year 2017
Language eng
Abstract This study aimed to identify the microRNAs associated with sclerotic status of subchondral bone in the pathogenesis of osteoarthritis (OA). Total RNA was extracted from non-sclerotic and sclerotic OA subchondral bone from patients undergoing knee replacement surgeries. miRCURY™ LNA miRNA chip and qRT-PCR were used to profile and validate differential microRNA expression. In addition, we further confirmed profiles of altered miRNAs in an OA rat meniscectomy animal model and their putative targets of the miRNAs were predicted using ingenuity (IPA) software. Finally, five short-listed miRNAs were reactivated by transient in vitro overexpression (miRNA mimics) in subchondral bone osteoblasts and their phenotypes were assessed. Functional screening identified 30 differentiated miRNAs in sclerotic subchondral bone compared to non-sclerotic bone of OA patients. Data integration resulted in confirmation of the eight miRNAs, with aberrant expression in independent human OA bone sample set. In silico analysis (IPA) identified 732 mRNA transcripts as putative targets of the eight altered miRNAs, of which twenty genes were validated to be differentially expressed in sclerotic compared to non-sclerotic bone samples. Out of eight dysregulated miRNA’s, five of them showed consistent time-dependent downregulation in a rat OA model. Furthermore, synthetic miR-199a-3p, miR-199a-5p, miR-590-5p, and miR-211-5p mimics rescued the abnormal osteoarthritic subchondral bone osteoblast gene expression and mineralization. We have identified four novel miRNAs that play important roles in subchondral bone pathogenesis in OA. Additional studies are required to develop these miRNAs into therapeutic modalities for OA.
Keyword MicroRNA
MRNA targets
Osteoarthritis
Profiling
Subchondral bone
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Australian Institute for Bioengineering and Nanotechnology Publications
 
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