Abstract
To better understand the molecular processes involved in driving osteoarthritis disease progression we characterized expression profiles of microRNAs (miRNA) and mRNAs in synovial tissue from a post-traumatic OA mouse model. OA was induced in 10–12 week old male C57BL6 mice by bilateral surgical destabilization of the medial meniscus (DMM). RNA isolated from the anterior synovium of mice at 1 and 6 weeks post-surgery was subject to expression profiling using Agilent microarrays and qPCR. OA severity was determined histologically. Anterior and posterior synovitis decreased with post-operative time after sham and DMM. No differences in synovitis parameters were evident between sham and DMM in the anterior synovium at either time. While expression profiling revealed 394 miRNAs were dysregulated between 1 and 6 week time-points in the anterior synovium, there were no significant changes in miRNA or mRNA expression between DMM and sham mice at both time-points. Bioinformatic analysis of the miRNAs and mRNAs differentially expressed in tandem with the resolution of anterior synovial inflammation revealed similar biological processes and functions, including organismal injury, connective tissue disorder and inflammatory responses. Our data demonstrates that early OA-specific patterns of synovial miRNAs or mRNAs dysregulation could not be identified in this model of post-traumatic OA.
Highlights
Critical need to perform parallel molecular studies on all OA-affected joint tissues to determine their pathophysiological contribution, and to compare with appropriate controls to define disease-specific mechanisms
This was accompanied by a significant increase in cartilage structural damage in the tibia but not the femur of 6 week destabilization of the medial meniscus (DMM) mice compared with sham and compared with week 1 DMM group (Fig. 1B)
Total anterior synovitis score decreased with post-operative time for both sham and DMM surgeries but there was no statistical difference between surgeries at either time-point (Fig. 2A)
Summary
Critical need to perform parallel molecular studies on all OA-affected joint tissues to determine their pathophysiological contribution, and to compare with appropriate controls to define disease-specific mechanisms In this regard, microRNAs (miRNAs) are being identified as novel regulators of cartilage homeostasis and OA pathology, making them exciting candidates for treatment and as diagnostic biomarkers[14,15,16,17,18]. We conducted parallel global miRNA and mRNA expression microarrays of synovium from DMM (“OA-inducing injury”) and sham-operated (“non-OA-inducing injury”) joints at 1 and 6 weeks post-surgery. These studies provide the first comprehensive transcriptome-wide analysis of temporal and disease-specific regulation of synovial mRNAs and their regulatory miRNAs in ptOA
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