Ultrasound induces cyclooxygenase-2 expression through integrin, integrin-linked kinase, Akt, NF-kappa B and p300 pathway in human chondrocytes

作者：Hsu Horng Chaung; Fong Yi Chin; Chang Chih Shiang; Hsu Chin Jung; Hsu Sheng Feng; Lin Jaung Geng; Fu Wen Mei; Yang Rong Sen; Tang Chih Hsin^*

来源：Cellular Signalling, 2007, 19(11): 2317-2328.

DOI：10.1016/j.cellsig.2007.07.006

• ultrasound
• COX-2
• chondrocyte
• integrin
• ILK
• NF-kappa B

It has been shown that ultrasound (US) stimulation accelerates fracture healing in the animal models and in clinical studies. However, the precise molecular events generated by US in chondrocytes have not been clarified well. Here we found that US stimulation transiently increased the surface expression of alpha 2, alpha 5, beta 1 or beta 3 but not alpha 3 or alpha 4 integrins in human chondrocytes, as shown by flow cytometric analysis. US stimulation increased prostaglandin E-2 formation as well as the protein and mRNA levels of cyclooxygenase-2 (COX-2). At the mechanistic level, anti-integrin beta 1 and beta 3 antibodies or beta 1 and beta 3 integrin small interference RNA attenuated the US-induced COX-2 expression. Integrin-linked kinase (ILK) inhibitor (KP-392), Akt inhibitor, NF-kappa B inhibitor (PDTC) or I kappa B protease inhibitor (TPCK) also inhibited the potentiating action of US. US stimulation promotes kinase activity of ILK, phosphorylation of Akt. In addition, US stimulation also induces IKK alpha/beta phosphorylation, 276 I kappa B alpha phosphorylation, IKB alpha degradation, p65 phosphorylation at Ser(276), p65 and p50 translocation from the cytosol to the nucleus, and kappa B-luciferase activity. The binding of p65 to the NF-kappa B element, as well as the recruitment of p300 and the enhancement of p50 acetylation on the COX-2 promoter was enhanced by US. Taken together, our results provide evidence that US stimulation increases COX-2 expression in chondrocytes via the integrin/ILK/Akt/NF-kappa B and p300 signaling pathway.

• 出版日期2007-11
• 单位中国医科大学