Journal of Inflammation (Jun 2019)

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

  • Qihong Que,
  • Xinghua Guo,
  • Longxin Zhan,
  • Shaodong Chen,
  • Zengli Zhang,
  • Xiaoming Ni,
  • Bin Ye,
  • Shuanglin Wan

DOI
https://doi.org/10.1186/s12950-019-0218-y
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 9

Abstract

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Abstract 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 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. Conclusions Together our results suggest that liraglutide exhibits anti-inflammatory activity through the activation of the PKA/CREB pathway in an OA rat model.

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