AMP-activated protein kinase (AMPK) is essential for maintaining energy balance and has a crucial role in various inflammatory pathways. In this study, AMPK levels positively correlated with many inflammatory indexes in RA patients, especially in the affected synovium. In RA sera, a positive correlation between p-AMPK-α1 levels and DAS28 activity (r = 0.270, p < 0.0001) was found. Similarly, a positive correlation was observed between AMPK-α1 and TNF-α levels (r = 0.460, p = 0.0002). Differentially expressed genes between OA and RA synovium from NCBI GEO profiles and our RNA sequencing data suggested activation of metabolic pathways specific to RA-FLS. AMPK-α1 was highly expressed in the synovium of RA but not OA patients. AMPK activator, metformin, inhibited FLS proliferation at higher but not lower concentrations, whereas the inhibitor, dorsmophin, promoted the proliferation of RA-FLS. Interestingly, both metformin and dorsmophin inhibited the migration of RA-FLS. After metformin treatment, expression of IL-6, TNF-α and IL-1β were significantly down regulated in RA-FLS, however, increased expression of (p)-AMPK-α1, PKA-α1 and HAPLN1 was observed. Increased level of HAPLN1 in RA-FLS by AMPK activator could potentially be beneficial in protecting the joints. Hence, our results demonstrate the potential of AMPK activator as a therapeutic for RA.

AMP激活的蛋白激酶（AMPK）对于维持能量平衡至关重要，并且在各种炎症途径中都起着至关重要的作用。在这项研究中，AMPK水平与RA患者尤其是受影响滑膜中的许多炎症指标呈正相关。在RA血清中，发现p-AMPK-α1水平与DAS28活性呈正相关（r = 0.270，p <0.0001）。同样，在AMPK-α1和TNF-α水平之间也观察到正相关（r = 0.460，p = 0.0002）。从NCBI GEO档案中获得的OA和RA滑膜之间的差异表达基因以及我们的RNA测序数据表明，RA-FLS特异性代谢途径的激活。AMPK-α1在RA的滑膜中高表达，而在OA患者中不高。AMPK激活剂二甲双胍在较高浓度但不较低浓度下抑制FLS增殖，而抑制剂 dorsmophin，促进RA-FLS的增殖。有趣的是，二甲双胍和多毛菌素均抑制RA-FLS的迁移。二甲双胍治疗后，RA-FLS中IL-6，TNF-α和IL-1β的表达明显下调，但观察到（p）-AMPK-α1，PKA-α1和HAPLN1的表达增加。AMPK激活剂可增加RA-FLS中HAPLN1的含量，可能对保护关节有益。因此，我们的结果证明了AMPK激活剂作为RA的治疗剂的潜力。AMPK激活剂可增加RA-FLS中HAPLN1的含量，可能对保护关节有益。因此，我们的结果证明了AMPK激活剂作为RA的治疗剂的潜力。AMPK激活剂可增加RA-FLS中HAPLN1的含量，可能对保护关节有益。因此，我们的结果证明了AMPK激活剂作为RA的治疗剂的潜力。