title: Mechanotransduction pathways of low-intensity ultrasound in C-28/I2 human chondrocyte cell line.
abstract: Low-intensity ultrasound (LIUS) has recently been considered to be an effective method to induce cartilage repair and/or regeneration after injury. Nevertheless, there is no study to provide a cellular mechanism or signal pathways of LIUS stimulation. The current study is designed to investigate the effects of LIUS on the mechanotransduction pathways in C-28/I2, an immortalized human chondrocyte cell line. C-28/I2 cells were treated with LIUS at an intensity of 200 mW/cm2 using Noblelife from Duplogen. The role of stretch-activated channels (SAC) and integrins that are most well-known mechanoreceptors on the chondrocyte cell surface was first examined in mediating the LIUS effects on the expression of type II collagen and aggrecan. When analysed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, gadolinium (a specific inhibitor of SACs) or GRGDSP (a peptide inhibitor of integrins) specifically reduced the LIUS-induced elevation of type II collagen and aggrecan expressions depending on the incubation time. In addition, the LIUS treatment of C-28/I2 cells induced the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) but not p38 kinase among the members of the mitogen-activated protein kinases (MAPKs). The phosphorylation of ERK by LIUS was repressed by a specific inhibitor of the ERK pathway and integrin function. These results suggest that the LIUS signal might be mediated via canonical mechanoreceptors of SACs and integrins and subsequently through JNK and ERK pathways. The present study provides the first evidence for the activation of the mechanotransduction pathways by LIUS in human chondrocytes.
authors.affiliation: Research Institute for Medical Sciences, Inha University College of Medicine, Incheon, Republic of Korea.
authors.forename: B H
authors.initials: BH
authors.lastname: Choi
authors.forename: M H
authors.initials: MH
authors.lastname: Choi
authors.forename: M-G
authors.initials: MG
authors.lastname: Kwak
authors.forename: B-H
authors.initials: BH
authors.lastname: Min
authors.forename: Z H
authors.initials: ZH
authors.lastname: Woo
authors.forename: S R
authors.initials: SR
authors.lastname: Park
mesh_terms: D002460:Cell Line; D019902:Chondrocytes / Q000502:physiology* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005109:Extracellular Matrix / Q000502:physiology* / Q000528:radiation effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology* / Q000528:radiation effects; D011829:Radiation Dosage; D013010:Sonication