Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 1 - PubMed (original) (raw)

. 2019 Oct 15;383(2):111556.

doi: 10.1016/j.yexcr.2019.111556. Epub 2019 Aug 12.

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Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 1

Takashi Ohtsuki et al. Exp Cell Res. 2019.

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Abstract

The synovial fluids of patients with osteoarthritis (OA) contain elevated levels of inflammatory cytokines, which induce the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and of the matrix metalloproteinase (MMP) in chondrocytes. Mechanical strain has varying effects on organisms depending on the strength, cycle, and duration of the stressor; however, it is unclear under inflammatory stimulation how mechanical strain act on. Here, we show that mechanical strain attenuates inflammatory cytokine-induced expression of matrix-degrading enzymes. Cyclic tensile strain (CTS), as a mechanical stressor, attenuated interleukin (IL)-1β and tumor necrosis factor (TNF)-α-induced mRNA expression of ADAMTS4, ADAMTS9, and MMP-13 in normal chondrocytes (NHAC-kn) and in a chondrocytic cell line (OUMS-27). This effect was abolished by treating cells with mechano-gated channel inhibitors, such as gadolinium, transient receptor potential (TRP) family inhibitor, ruthenium red, and with pharmacological and small interfering RNA-mediated TRPV1 inhibition. Furthermore, nuclear factor κB (NF-κB) translocation from the cytoplasm to the nucleus resulting from cytokine stimulation was also abolished by CTS. These findings suggest that mechanosensors such as the TRPV protein are potential therapeutic targets in treating OA.

Keywords: ADAMTS; Chondrocyte; Mechanosensor; Osteoarthritis; TRP.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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