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Blocker Targeting MicroRNA-181a-5p Successfully Treats Knee, Spine OA
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A blocker consisting of locked nucleic acid antisense oligonucleotides, targeting the biomarker microRNA-181a-5p, is successful in protecting cartilage in spine and knee osteoarthritis, according to data published in the Annals of the Rheumatic Diseases.
“In 2016, our group identified a molecule, namely microRNA-181a-5p, which is not only highly elevated in the cartilage of patients with facet joint osteoarthritis, but also plays an active role in cartilage degeneration,” Mohit Kapoor, PhD, director of arthritis research at University Health Network in Toronto, told Healio Rheumatology. “Since then, efforts have been put in testing whether blocking microRNA-181a-5p could help stop cartilage damage in facet joints and other joints including the knee.”
To determine if locked nucleic acid microRNA-181a-5p antisense oligonucleotides could limit articular cartilage damage, Kapoor and colleagues used a variety of experimental models, including animal models and human tissue samples of facet joint and knee osteoarthritis. In addition, the researchers used istopathological analysis, including immunohistochemistry and in situ hybridization, to detect key osteoarthritis catabolic markers and microRNA, respectively.
Kapoor and colleagues also analyzed apoptotic and cell death markers by flow cytometry, and applied qPCR and immunoblotting to quantify gene and protein expression.
According to the researchers, microRNA-181a-5p expression was increased in human facet joint and knee cartilage in osteoarthritis, as well as injury-induced facet joints osteoarthritis in rats and trauma-induced knee osteoarthritis cartilage in mice, compared with the control cartilage. Locked nucleic acid microRNA-181a-5p antisense oligonucleotides in rat and mouse chondrocytes reduced cartilage catabolic and chondrocyte apoptotic and cell death markers in vitro.
In addition, treatment of osteoarthritis-induced rat facet joint, or mouse knee joints, with intra-articular injections of in vivo grade locked nucleic acid microRNA-181a-5p antisense oligonucleotides attenuated cartilage destruction, and the expression of catabolic, hypertrophic, apoptotic/cell death and type II collagen breakdown markers. Treatment of locked nucleic acid microRNA-181a-5p antisense oligonucleotides in cultures of human knee osteoarthritis chondrocytes, in vitro, as well as cartilage explants, ex vivo, also demonstrated cartilage protective effects.
“The results show that the local injection of microRNA-181a-5p blocker in preclinical animal models of spine and knee joints is able to slow down the process of cartilage destruction,” researcher Akihiro Nakamura, MD, of the Arthritis Program at University Health Network, told Healio Rheumatology. “Furthermore, treatment of human cells/tissues derived from osteoarthritis patients with microRNA-181a-5p blocker is able to decrease the production of harmful molecules that destroy cartilage. Our team is now determining the safety of this treatment to initiate clinical trials in the near future.” – by Jason Laday
Disclosure: Kapoor reports grants from the Krembil Foundation, the Canadian Institute of Health Research and the Campaign to Cure Arthritis via the Toronto General and Western Foundation, University Health Network. Please see the study for all other authors’ relevant financial disclosures.
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