Scheike Ann-Sofie, Plomp Saskia, Fugazzola Maria Carlotta, Meurot Coralie, Berenbaum Francis, van Weeren Paul René, Tryfonidou Marianna Andriana, von Hegedus Johannes Hendrick
Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
4Moving Biotech, Lille, France.
J Orthop Res. 2025 May;43(5):893-903. doi: 10.1002/jor.26050. Epub 2025 Feb 4.
This study investigates the anti-inflammatory properties of liraglutide, a glucagon-like peptide 1 receptor agonists, in equine in vitro models and in an in vivo acute synovitis model in Shetland ponies. The anti-inflammatory effect of liraglutide was assessed by measuring concentrations of inflammatory biomarker C-C Motif Chemokine Ligand 2 (CCL2) in culture media of equine whole blood, peripheral blood mononuclear cells (PBMCs), chondrocytes, and synoviocytes, with or without lipopolysaccharide (LPS) or interleukin-1β. In the in vivo experiment, acute synovitis was bilaterally induced with 0.25 ng LPS in the intercarpal joints of seven healthy Shetland ponies. The ponies were subsequently treated with either 6 mg liraglutide or a placebo as a paired control in each joint. The impact of liraglutide on biomarkers associated with inflammation (including white blood cell count, total protein, CCL2, and bradykinin) and cartilage metabolism (such as glycosaminoglycans, general matrix metalloproteinase activity, carboxypropeptide type II collagen, and collagen-cleavage neoepitope of type II collagen) was assessed across serial synovial fluid samples. Liraglutide was found to have an anti-inflammatory effect by reducing CCL2 concentrations in culture media of whole blood, PBMCs, chondrocytes, and synoviocytes. In contrast, no significant differences in synovial fluid inflammatory nor cartilage metabolism biomarker levels were found between joints treated with LPS and 6 mg liraglutide, versus LPS and placebo. In conclusion, liraglutide demonstrates the potential to attenuate inflammatory processes in joint cells. Additional research is necessary to validate its efficacy within the complex milieu of an inflamed joint.
本研究在马的体外模型以及设得兰矮种马的体内急性滑膜炎模型中，探究了胰高血糖素样肽-1受体激动剂利拉鲁肽的抗炎特性。通过测量马全血、外周血单核细胞（PBMC）、软骨细胞和滑膜细胞培养基中炎症生物标志物C-C基序趋化因子配体2（CCL2）的浓度，评估利拉鲁肽在有或无脂多糖（LPS）或白细胞介素-1β情况下的抗炎效果。在体内实验中，对7匹健康的设得兰矮种马的腕间关节双侧注射0.25 ng LPS诱导急性滑膜炎。随后，在每个关节中，对这些矮种马分别用6 mg利拉鲁肽或安慰剂进行配对对照治疗。通过一系列滑膜液样本，评估利拉鲁肽对与炎症相关的生物标志物（包括白细胞计数、总蛋白、CCL2和缓激肽）以及软骨代谢（如糖胺聚糖、一般基质金属蛋白酶活性、II型胶原羧基端前肽和II型胶原的胶原裂解新表位）的影响。结果发现，利拉鲁肽通过降低全血、PBMC、软骨细胞和滑膜细胞培养基中的CCL2浓度而具有抗炎作用。相比之下，在注射LPS并用6 mg利拉鲁肽治疗的关节与注射LPS并用安慰剂治疗的关节之间，滑膜液炎症生物标志物水平和软骨代谢生物标志物水平均未发现显著差异。总之，利拉鲁肽显示出减轻关节细胞炎症过程的潜力。有必要进行更多研究以验证其在炎症关节复杂环境中的疗效。
