TY - JOUR T1 - microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 111 LP - 121 DO - 10.1136/annrheumdis-2018-213629 VL - 78 IS - 1 AU - Akihiro Nakamura AU - Yoga Raja Rampersaud AU - Sayaka Nakamura AU - Anirudh Sharma AU - Fanxing Zeng AU - Evgeny Rossomacha AU - Shabana Amanda Ali AU - Roman Krawetz AU - Nigil Haroon AU - Anthony V Perruccio AU - Nizar N Mahomed AU - Rajiv Gandhi AU - Jason S Rockel AU - Mohit Kapoor Y1 - 2019/01/01 UR - http://ard.bmj.com/content/78/1/111.abstract N2 - Objectives We recently identified microRNA-181a-5p (miR-181a-5p) as a critical mediator involved in the destruction of lumbar facet joint (FJ) cartilage. In this study, we tested if locked nucleic acid (LNA) miR-181a-5p antisense oligonucleotides (ASO) could be used as a therapeutic to limit articular cartilage degeneration.Methods We used a variety of experimental models consisting of both human samples and animal models of FJ and knee osteoarthritis (OA) to test the effects of LNA-miR-181a-5p ASO on articular cartilage degeneration. Histopathological analysis including immunohistochemistry and in situ hybridisation were used to detect key OA catabolic markers and microRNA, respectively. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR and immunoblotting were applied to quantify gene and protein expression.Results miR-181a-5p expression was increased in human FJ OA and knee OA cartilage as well as injury-induced FJ OA (rat) and trauma-induced knee OA (mouse) cartilage compared with control cartilage, correlating with classical OA catabolic markers in human, rat and mouse cartilage. We demonstrated that LNA-miR-181a-5p ASO in rat and mouse chondrocytes reduced the expression of cartilage catabolic and chondrocyte apoptotic/cell death markers in vitro. Treatment of OA-induced rat FJ or mouse knee joints with intra-articular injections of in vivo grade LNA-miR-181a-5p ASO attenuated cartilage destruction, and the expression of catabolic, hypertrophic, apoptotic/cell death and type II collagen breakdown markers. Finally, treatment of LNA-miR-181a-5p ASO in cultures of human knee OA chondrocytes (in vitro) and cartilage explants (ex vivo) further demonstrated its cartilage protective effects.Conclusions Our data demonstrate, for the first time, that LNA-miR-181a-5p ASO exhibit cartilage-protective effects in FJ and knee OA. ER -