Mechanical force induces type I collagen expression in human periodontal ligament fibroblasts through activation of ERK/JNK and AP‐1

Abstract

Type I collagen (COL I) is the predominant collagen in the extracellular matrix of periodontal ligament (PDL), and its expression in PDL fibroblasts (PLF) is sensitive to mechanical force. However, the mechanism by which PLF induces COL I to respond to mechanical force is unclear. This study examined the nature of human PLF in mediating COL I expression in response to centrifugal force. Signal transduction pathways in the early stages of mechanotransduction involved in the force-driven regulation of COL I expression were also investigated. Centrifugal force up-regulated COL I without cytotoxicity and activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase. ERK and JNK inhibitor blocked the expression of COL I but p38 kinase inhibitor had no effect. Centrifugal force activated activator protein-1 (AP-1) through dimerization between c-Fos and c-Jun transcription factors. ERK and JNK inhibitors also inhibited AP-1-DNA binding, c-Fos nuclear translocation, and c-Jun phosphorylation that were increased in the force-exposed PLF. Further, transfecting the cells with c-Jun antisense oligonucleotides almost completely abolished the force-induced increase of c-Jun phosphorylation and COL I induction. Our findings suggest that mechanical signals are transmitted into the nucleus by ERK/JNK signaling pathways and then stimulate COL I expression through AP-1 activation in force-exposed human PLF.

Peripheral and Spinal Mechanisms of Pain and Dry Needling Mediated Analgesia: A Clinical Resource Guide for Health Care Professionals

“…Finally, mechanical stimulation of fibroblasts results in collagen synthesis via activation of mitogen activated protein kinases (MAPK). MAPK, the most prominent kinase activated by mechanotransduction, initiates the extracellular signal regulated-kinase ½ (ERK½) pathway [117]. ERK stimulates the production of Type-1 collagen fibers via transcription factors such as activator protein-1 [115,117].…”

“…MAPK, the most prominent kinase activated by mechanotransduction, initiates the extracellular signal regulated-kinase ½ (ERK½) pathway [117]. ERK stimulates the production of Type-1 collagen fibers via transcription factors such as activator protein-1 [115,117]. Interestingly, a recent study by Park et al found that DN at GB34 turned on 236 genes secondary to the ERK cascade [118].…”

Effect of CXCR4 inhibitor AMD3100 on alkaline phosphatase activity and mineralization in osteoblastic MC3T3-E1 cells

“…For Western-blot analysis, MC3T3-E1 cells at 3, 6, 9, and 14 days of osteogenic induction were collected, and then whole cell lysate was obtained and the amount of total cellular protein was determined using the Bradford assay (15,22). Equal loading of 30 μg aliquots of total protein from each sample were fractionated on 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the following that treatment with CXCR4 antagonist AMD3100 decreased osteogenic media-induced ALP activity in a concentration-dependent manner (49%, 56%, 67%, and 77% decreases with 50, 100, 200, and 400 μM of AMD3100, respectively) (data not shown).…”

Induction of caspase-dependent apoptosis in melanoma cells by the synthetic compound (E)-1-(3,4-dihydroxyphenethyl)-3-styrylurea

“…Primary cultures of hGF and hPLF were also used as control cells (20,21). This study was approved by the Review Board of Chonbuk National University Hospital (CNUH).…”

“…Protein lysates were prepared in lysis buffer as described elsewhere (21), and each protein (30 μg) sample were separated by 12% SDS-PAGE and blotted onto PVDF membranes. The blots were probed with primary and secondary antibodies and then developed by enhanced chemiluminescence (Amersham Pharmacia Biotech, Buckinghamshire, UK) immediately before exposure to X-ray film (Eastman-Kodak, Rochester, NY, USA).…”