Mechanical force induces type I collagen expression in human periodontal ligament fibroblasts through activation of ERK/JNK and AP-1.
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.
Kook
Sung-Ho
SH
Division of Biological Sciences, Chonbuk National University, Jeonju 561-756, South Korea.
Hwang
Jung-Min
JM
Park
Jong-Sun
JS
Kim
Eun-Mi
EM
Heo
Jung-Sun
JS
Jeon
Young-Mi
YM
Lee
Jeong-Chae
JC
D000328:Adult; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology*; D013314:Stress, Mechanical; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D024042:Collagen Type I; D016376:Oligonucleotides, Antisense; D018808:Transcription Factor AP-1; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases