Wanlop KunanusornchaiChatchai MuanprasatVaranuj ChatsudthipongMahidol University2018-12-112019-03-142018-12-112019-03-142016-12-01Molecular and Cellular Biochemistry. Vol.423, No.1-2 (2016), 175-18515734919030081772-s2.0-84989205098https://repository.li.mahidol.ac.th/handle/20.500.14594/42348© 2016, Springer Science+Business Media New York. Joint mobilization is known to be beneficial in osteoarthritis (OA) patients. This study aimed to investigate the effect of stretching on adenosine monophosphate-activated protein kinase (AMPK) activity and its role in modulating inflammation in rabbit synovial fibroblasts. Uniaxial stretching of isolated rabbit synovial fibroblasts for ten min was performed. Stretching-induced AMPK activation, its underlying mechanism, and its anti-inflammatory effect were investigated using Western blot. Static stretching at 20 % of initial length resulted in AMPK activation characterized by expression of phosphorylated AMPK and phosphorylated acetyl-Co A carboxylase. AMP-activated protein kinase phosphorylation peaked 1 h after stretching and declined toward resting activity. Using cell viability assays, static stretching did not appear to cause cellular damage. Activation of AMPK involves Ca2+ influx via a mechanosensitive L-type Ca2+ channel, which subsequently raises intracellular Ca2+ and activates AMPK via Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ). Interestingly, stretching suppressed TNFα-induced expression of COX-2, iNOS, and phosphorylated NF-κB. These effects were prevented by pretreatment with compound C, an AMPK inhibitor. These results suggest that mechanical stretching suppressed inflammatory responses in synovial fibroblasts via a L-type Ca2+-channel-CaMKKβ-AMPK-dependent pathway which may underlie joint mobilization’s ability to alleviate OA symptoms.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1007/s11010-016-2835-6