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.
Highlights
Osteoarthritis (OA) is the most common chronic disorder affecting the joints and constitutes a major burden on public health
It is believed that the articular cartilage—which consists of chondrocytes and extracellular matrix (ECM) molecules including aggrecan, collagen, and hyaluronan (HA) [1,2]—in patients with OA is destroyed by the aberrant up-regulation of matrix-degrading proteinases; it has been demonstrated that the synovial fluid contains elevated levels of inflammatory cytokines [3] that induce expression and activity of matrix metalloproteinase (MMP), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) [4,5,6,7]
We examined whether mechanical strain attenuates expression of ADAMTS4, ADAMTS9, and MMP13 induced by IL-1β and tumor necrosis factor α (TNF-α) in OUMS-27 cells
Summary
Osteoarthritis (OA) is the most common chronic disorder affecting the joints and constitutes a major burden on public health. It is believed that the articular cartilage—which consists of chondrocytes and extracellular matrix (ECM) molecules including aggrecan, collagen, and hyaluronan (HA) [1,2]—in patients with OA is destroyed by the aberrant up-regulation of matrix-degrading proteinases; it has been demonstrated that the synovial fluid contains elevated levels of inflammatory cytokines [3] that induce expression and activity of matrix metalloproteinase (MMP), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) [4,5,6,7]. In cartilage affected by OA, aggrecan and collagen are degraded [5]. We recently reported that inflammatory cytokines induce the expression of ADAMTS9 to a greater extent than that of ADAMTS4 and of ADAMTS5 in chondrocytes [6], suggesting that ADAMTS9 plays an important role in developing OA.
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