The GLP-1 agonist, liraglutide, ameliorates inflammation through the activation of the PKA/CREB pathway in a rat model of knee osteoarthritis

作者：Qihong Que, Xinghua Guo, Longxin Zhan, Shaodong Chen, Zengli Zhang, Xiaoming Ni, Bin Ye, Shuanglin Wan · 发表于：Journal of Inflammation · 年份：2019 · DOI：10.1186/s12950-019-0218-y · 被引用次数：85 · 研究领域：Osteoarthritis Treatment and Mechanisms、Diabetes Treatment and Management、Pain Mechanisms and Treatments

BACKGROUND: Inflammation is a common pathological phenomenon of osteoarthritis (OA). Accumulated evidence indicates that ameliorating or suppressing inflammation might be a promising and effective therapeutic strategy for the treatment of OA. Notably, glucagon-like peptide-1 (GLP-1)-based drugs are being successfully used to control glucose levels in patients with diabetes mellitus. In addition, recent findings have indicated that GLP-1 agonists, such as liraglutide have therapeutic potential in preventing inflammation-related disorders through the regulation of protein kinase A (PKA)/ cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signals. Intra-articular injection of monoiodoacetate (MIA) has been widely used to induce OA. Thus, the present study aimed to investigate whether liraglutide has anti-inflammatory effects on MIA-induced OA rats and uncover its underlying molecular mechanisms. METHODS: Intra-articular injection of MIA was used to induce knee OA in a rat model. Subcutaneous injection of liraglutide was used to upregulate the expression of GLP-1 receptor (GLP-1R). Western blot analysis was utilized to measure the expression of GLP-1R, PKA/CREB pathway components and inflammation-related proteins, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6. Immunoprecipitation techniques were used to detect the interactions between GLP-1R and the PKA/CREB pathway. RESULTS: The levels of GLP-1R decreased significant...