Abstract
BackgroundInflammation 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.MethodsIntra-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.ResultsThe levels of GLP-1R decreased significantly in the knees of OA rats, accompanied by the downregulation of PKA /CREB signals and upregulation of inflammation-related proteins. We also found that GLP-1R interacted with the PKA/CREB pathway and that liraglutide could activate PKA/CREB signals, thereby inhibiting the expression of inflammation-related proteins.ConclusionsTogether our results suggest that liraglutide exhibits anti-inflammatory activity through the activation of the PKA/CREB pathway in an OA rat model.
Highlights
Inflammation is a common pathological phenomenon of osteoarthritis (OA)
Rabbit anti-GLP-1 receptor (GLP-1R), protein kinase A (PKA), phospho-PKA (Thr197), cAMP response elementbinding protein (CREB), phospho-CREB (Ser 133), tumor necrosis factoralpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 primary antibodies were purchased from Abcam (Cambridge, UK)
GLP-1R is involved in the PKA/CREB pathway of cartilage tissues in the knee OA rat model In this study, we conducted immunoprecipitation analysis to detect protein-protein interactions
Summary
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. The present study aimed to investigate whether liraglutide has anti-inflammatory effects on MIA-induced OA rats and uncover its underlying molecular mechanisms. Osteoarthritis (OA) is one of the most prevalent and debilitating joint diseases. It is pathologically characterized by loss of articular cartilage, hypertrophic bone changes, osteophyte formation, subchondral bone remodeling and low-grade synovial inflammation. It is clinically characterized by joint pain, nighttime pain, functional impairment and limited movement [1, 2]. It is crucial to elucidate the precise underlying molecular mechanisms mediating its development in order to find novel, efficacious and promising therapeutic modalities for OA
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