A2AR regulate inflammation through PKA/NF-κB signaling pathways in intervertebral disc degeneration

作者：Weijun Liu, Qingbo Li, Weizhi Fang, Lei Cai, Zhengkun Wang, Bowen Kou, Chuankun Zhou, Yichi Zhou, Zhi Yao, Mengcheng Wei, Shishuang Zhang · 发表于：European journal of medical research · 年份：2024 · DOI：10.1186/s40001-024-02028-7 · 被引用次数：16 · 研究领域：Pain Mechanisms and Treatments、Pregnancy-related medical research、Adenosine and Purinergic Signaling

Reduction of inflammatory damage and inhibition of nucleus pulposus (NP) apoptosis are considered to be the main effective therapy idea to reverse the intervertebral disc degeneration (IDD) and alleviate the chronic low back pain. The adenosine A2A receptor (A2AR), as a member of G protein-coupled receptor families, plays an important role in the anti-inflammation and relieving pain. So far, the impact of A2AR on IDD therapy is unclear. The aim of this study was to explore the role of Adenosine A 2A receptor (A 2A R) in the intervertebral disc degeneration (IDD) and clarify potential mechanism. IL-1β and acupuncture was used to establish IDD model rats. A 2A R agonist CGS-21680 and A 2A R antagonist SCH442416 were used to investigate the therapeutical effects for IDD. Histological examination, western blotting analysis and RT-PCR were employed to evaluate the the association between A 2A R and cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway. A 2A R activity of the intervertebral disc tissues was up-regulated in feedback way, and cAMP, PKA and CREB expression were also increased. But in general, IL-1β-induced IDD promoted the significant up-regulation the expression of inflammatory factors. The nucleus pulposus (NP) inflammation was exacerbated in result of MMP3 and Col-II decline through activating NF-κB signaling pathway. A 2A R agonist CGS-21680 exhibited a disc protective effect through significantly increasing A 2A R activity, then further activated c...