Liraglutide, a glucagon-like peptide 1 receptor agonist, exerts analgesic, anti-inflammatory and anti-degradative actions in osteoarthritis
C Meurot, C Martin, L Sudre, J Breton, C Bougault, R Rattenbach, K Bismuth, C Jacques, F Berenbaum, C Meurot, C Martin, L Sudre, J Breton, C Bougault, R Rattenbach, K Bismuth, C Jacques, F Berenbaum
Abstract
Osteoarthritis (OA) is a common disabling disease worldwide, with no effective and safe disease-modifying drugs (DMOAD) in the market. However, studies suggest that drugs, such as liraglutide, which possess strong potential in decreasing low-grade systemic inflammation may be effective in treating OA. Therefore, the aim of this study was to examine the anti-inflammatory, analgesic, and anti-degradative effects in OA using in vitro and in vivo experiments. The results showed that intra-articular injection of liraglutide alleviated pain-related behavior in in vivo sodium monoiodoacetate OA mouse model, which was probably driven by the GLP-1R-mediated anti-inflammatory activity of liraglutide. Moreover, liraglutide treatment significantly decreased IL-6, PGE2 and nitric oxide secretion, and the expression of inflammatory genes in vitro in chondrocytes and macrophages in a dose-dependent manner. Additionally, liraglutide shifted polarized macrophage phenotype in vitro from the pro-inflammatory M1 phenotype to the M2 anti-inflammatory phenotype. Furthermore, liraglutide exerted anti-catabolic activity by significantly decreasing the activities of metalloproteinases and aggrecanases, a family of catabolic enzymes involved in cartilage breakdown in vitro. Overall, the findings of this study showed that liraglutide ameliorated OA-associated pain, possess anti-inflammatory and analgesic properties, and could constitute a novel therapeutic candidate for OA treatment.
Conflict of interest statement
Dr. Berenbaum reports personal fees from AstraZeneca, Boehringer, Bone Therapeutics, CellProthera, Expanscience, Galapagos, Gilead, Grunenthal, GSK, Eli Lilly, Merck Sereno, MSD, Nordic Pharma, Nordic Bioscience, Novartis, Pfizer, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, 4P Pharma, grants from TRB Chemedica; In addition. Dr Berenbaum is the CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. Dr. Rattenbach is the CEO of 4P Pharma and the chairwoman of 4Moving Biotech. 4Moving Biotech and Sorbonne University own 2 patents for method of use of GLP1 analogs in the treatment of osteoarthritis (PCT/FR2013/051998 and PCT/IB2018//059100).
© 2022. The Author(s).
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