RT Journal Article
SR Electronic
T1 Cartilage microRNA dysregulation during the onset and progression of mouse osteoarthritis overlaps with patient disease candidates
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 113456
DO 10.1101/113456
A1 Louise H.W. Kung
A1 Varshini Ravi
A1 Lynn Rowley
A1 Constanza Angelucci
A1 Amanda J. Fosang
A1 Katrina M. Bell
A1 Christopher B. Little
A1 John F. Bateman
YR 2017
UL http://biorxiv.org/content/early/2017/03/03/113456.abstract
AB The regulatory interplay between the joint cartilage and subchondral bone (SCB) is known be important in osteoarthritis (OA) pathology. Thus, to explore the role of microRNAs in osteoarthritis, we conducted global microRNA microarray expression profiling on microdissected medial tibial cartilage and SCB in a mouse model of OA produced by medial meniscus destabilization (DMM). Compared to sham-operated mice, DMM-operated mice had characteristic cartilage degeneration, SCB sclerosis and osteophyte formation. miRNA expression profiling revealed no statistically significant dysregulation of SCB miRNAs between DMM and sham-operated mice. In contrast, 139 miRNAs were found to be differentially expressed in DMM cartilage at 1 or 6 weeks post-surgery. To prioritize OA-candidates, dysregulated miRNAs were filtered against miRNAs identified in human OA and then using paired miRNA:mRNA expression analysis we identified a cohort of down-regulated microRNAs (miR-15a/16, 26b, 30c, 98, 149, 210, 342, 140, Let-7e) with corresponding changes in predicted target transcripts. Comparisons with microRNA dysregulation in DMM mouse cartilage where aggrecan cleavage was genetically ablated demonstrated that all, except Let-7e, were independent of aggrecan breakdown, earmarking this cohort of microRNAs of relevance to the critical early stages of OA initiation.