Adenosine monophosphate-activated protein kinase activation and suppression of inflammatory response by cell stretching in rabbit synovial fibroblasts.
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.
Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok, 10400, Thailand.
Wanlop
W
Kunanusornchai
Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok, 10400, Thailand.
Chatchai
C
Muanprasat
Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok, 10400, Thailand. varanuj.cha@mahidol.ac.th.
Varanuj
V
Chatsudthipong
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011817:Rabbits; D013583:Synovial Membrane / Q000201:enzymology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020746:Calcium Channels, L-Type; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases
AMPK; Inflammation; Mechanical stretch; NF-κB; Osteoarthritis; Synoviocyte
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