Biomechanical strain regulates TNFR2 but not TNFR1 in TMJ cells

Abstract

We sought to examine whether cyclic tensile strain (CTS) regulates the gene expression of tumor necrosis factor (TNF)-alpha, its receptors TNFR1 and TNFR2, and inducible nitric oxide synthase (iNOS) under inflammatory conditions, and whether these effects of CTS are sustained. Rat temporomandibular joint disc cells (TDC) were exposed to CTS in the presence or absence of interleukin (IL)-1beta for 4 and 24 h. Cells were also stimulated with IL-1beta for 24 h while being subjected to CTS only for the initial 1, 2, 4, 8, and 12 h or the entire 24 h incubation time. Furthermore, cells were incubated with IL-1beta for 24, 36, or 48 h while being exposed to CTS only for the initial 8 h. Gene expression of TNF-alpha, its receptors, and iNOS was analyzed by RT-PCR, whereas protein synthesis was determined by ELISA for TNF-alpha, immunofluorescence for TNFRs, and Griess reaction for nitric oxide. CTS inhibited the IL-1beta-stimulated synthesis of TNF-alpha, TNFR2, and iNOS. TNFR1 was constitutively expressed but not regulated by IL-1beta or CTS. Application of CTS for only 1 or 2 h during a 24 h incubation with IL-1beta was sufficient to inhibit IL-1beta-induced upregulation of TNF-alpha, TNFR2, and iNOS. However, for maximal inhibition of these genes a longer exposure of CTS was required. These findings are the first to show that biomechanical signals regulate the expression of TNFR2 but not TNFR1 under inflammatory conditions. Furthermore, the antiinflammatory effects of biomechanical signals on TDC are maintained for prolonged periods of time but are transient.

Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

“…In particular, low-level strain has generally been observed to block the expression of inflammation-related genes that augment cartilage destruction. 87 , 132 , 134 , 137 , 142 , 147 , 149 , 150 For example, using high frequency and low strain (3% elongation at 25 MHz), IL1 pro-inflammatory activity was inhibited, due to block of IL1-mediated NF-κB nuclear translocation, 134 in a transforming growth factor-β-activated kinase-1 (TAK1)-dependent fashion. 156 This prevented subsequent transcription of inflammatory gene targets, which normally result from NF-κB activation.…”

Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage

“…While different these cell-based configurations can help explain possible inhibitory mechanisms when loading intact cartilage using our METS. Agarwal et al16,19–21,39 reported that tensile strain (3%, 20%) inhibited or reduced IL-1-induced increases in gene expression (mRNA) for nitric oxide (NO), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, cyclo-oxygenase (COX)-2, and MMP-3, 7, 8, 9, 13, 16, 17 and 19, had no affect on MMP-2, 11 and 14 and TIMP-1, 2 and 3, and reversed IL-1 inhibition of aggrecan synthesis. They concluded that the tensile strain acts at multiple sites within the NF-κB signaling pathway.…”

Biomarkers for Temporomandibular Disorders: Current Status and Future Directions

“…Based on another research conducted on rat TMJ disc cells, which was exposed to cyclic tensile strain, it was found that the expression of TNFR2 was regulated by biomechanical signals regulate. However, this regulation did not occur to TNFR1 under inflammatory conditions [122].…”