저강도 초음파 자극이 사람 관절연골세포의 mechanotransduction pathway에 미치는 영향

초록

Adequate stimulation of chondrocyte to synthesize extracellular matrix to repair articular cartilage defect is key factor for osteoarthritis therapy. We have previously reported that low-intensity ultrasound (LIUS) enhanced metabolism of chondrocytes in vitro. However, the means by which mechanical stimuli are recognized by chondrocytes and how these signals are transduced into biochemical responses are poorly understood. In the present study, we evaluated the possible mechanotransduction pathway in LIUS stimulation (100mW/cm2intensity, 0.8MHz frequency) with immortalized human chondrocytes (C-28/I2). LIUS upregulated the expression of collagen type II at mRNA and protein levels in time-dependent manner, which was maximal at 0 time after US stimulation. Gadolinium, blocker of stretch-activated ion channel inhibit the increasing of collagen type II expression. Roles for integrins after US stimulation became evident by showing that integrin inhibitor GRGDSP inhibit the collagen type II. JNK phosphorylation was increased above basal level after US stimulation. This study provides the first evidence for the activation of the US-activated mechanotransduction pathway. LIUS can enhanced collagen type II synthesis by time dependent manner. LIUS is likely to use the stretch-activated ion channel and integrin as a mechanoreceptor, sequentially activating JNK pathway.