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.