Statement of Purpose: MicroRNAs (miR) are short, non-coding segments of RNA that play a vital role in post-transcriptional gene regulation by binding to mRNA and preventing translation. Several studies have demonstrated that miRNA are regulated during the progression of osteoarthritis (OA) via agonistic or antagonistic mechanisms. OA is characterized by an increased production of inflammatory cytokines and matrix degrading enzymes such as matrix metalloproteinase 13 (MMP-13). These catabolic cytokines, most notably interleukin-1 beta (IL-1β), signal in an autocrine and paracrine manner, stimulating their own production and the production of catabolic pathway mediators. Interrupting these pathways through miR regulation could provide a novel approach that targets the underlying biological mechanism driving the disease progression. miR-122 and mi-451 are produced by rat articular chondrocytes (rArCs); miR-122 stimulates proliferation whereas miR-451 inhibits proliferation and stimulates production of the catabolic enzyme, matrix metalloproteinase 13 (MMP-13). The aim of this study was to determine if adding miR-122 or inhibiting miR-451 would have a protective effect on the production of inflammatory mediators and how endogenous levels of these two microRNA change in OA in vivo.