Mechanical Stress Induce PG-E2 in Murine Synovial Fibroblasts Originating from the Temporomandibular Joint

Abstract

Genetic predisposition, traumatic events, or excessive mechanical exposure provoke arthritic changes in the temporomandibular joint (TMJ). We analysed the impact of mechanical stress that might be involved in the development and progression of TMJ osteoarthritis (OA) on murine synovial fibroblasts (SFs) of temporomandibular origin. SFs were subjected to different protocols of mechanical stress, either to a high-frequency tensile strain for 4 h or to a tensile strain of varying magnitude for 48 h. The TMJ OA induction was evaluated based on the gene and protein secretion of inflammatory factors (Icam-1, Cxcl-1, Cxcl-2, Il-1ß, Il-1ra, Il-6, Ptgs-2, PG-E2), subchondral bone remodelling (Rankl, Opg), and extracellular matrix components (Col1a2, Has-1, collagen and hyaluronic acid deposition) using RT-qPCR, ELISA, and HPLC. A short high-frequency tensile strain had only minor effects on inflammatory factors and no effects on the subchondral bone remodelling induction or matrix constituent production. A prolonged tensile strain of moderate and advanced magnitude increased the expression of inflammatory factors. An advanced tensile strain enhanced the Ptgs-2 and PG-E2 expression, while the expression of further inflammatory factors were decreased. The tensile strain protocols had no effects on the RANKL/OPG expression, while the advanced tensile strain significantly reduced the deposition of matrix constituent contents of collagen and hyaluronic acid. The data indicates that the application of prolonged advanced mechanical stress on SFs promote PG-E2 protein secretion, while the deposition of extracellular matrix components is decreased.

Mechanical Stress Induces Sodium Entry and Osmoprotective Responses in Murine Synovial Fibroblasts

“…With compressive strain, there was an increase in Il6 gene expression and IL6 protein secretion, while expression decreased with intermittent tension. These findings are in line with the literature [ 43 , 44 , 58 ].…”

“…The inflammatory mediators IL6, PTGS2, and PGE 2 have already been described in connection with OA in relation to catabolic processes [ 24 , 25 , 26 , 27 , 57 ]. An increased secretion of PGE 2 was demonstrated in murine synovial fibroblasts of the temporomandibular joint and osteoblasts of the subchondral bone exposed to mechanical stress [ 44 , 57 , 58 ]. Increased expression of inflammatory factors occurs particularly during short periods of intense mechanical stress, similar to the initial stage of OA.…”

“…The qPCR protocol basically followed the previously published proceedings [ 41 , 44 ]. Briefly, RNA was extracted using RNA-Solv (R6830-01, VWR, Darmstadt, Germany) according to the manufacturer’s protocol.…”

Effects of mechanical strain on periodontal ligament fibroblasts in presence of Aggregatibacter actinomycetemcomitans lysate

“…Contrary to previous results [ 43 ], RANKL gene expression was not downregulated after tensile strain in this study. In another recent study, the authors observed a trend for increased RANKL gene expression which was then associated with a reduced RANKL secretion [ 44 ]. Interestingly, the bacterial stimuli showed opposite tendencies on bone metabolism.…”

Mechanical Stretch Induced Skin Regeneration: Molecular and Cellular Mechanism in Skin Soft Tissue Expansion

“…Keratinocytes express CXCL1, CXCL2, CXCL8, and CCL20, which recruit neutrophils and are up-regulated in psoriasis to increase inflammation [ 87 ]. CXCL1, CXCL2, and CXCL8 are mechanoresponsive proteins that are up-regulated by mechanical stimulation in keratinocytes and fibroblasts [ 88 , 89 , 90 ]. CXCR2, a G-protein-coupled receptor, is a common receptor for CXCL1, CXCL2, and CXCL8, which can promote keratinocyte proliferation and angiogenesis [ 91 , 92 ].…”