tailieunhanh - Báo cáo y học: "Mechanical signals control SOX-9, VEGF, and c-Myc expression and cell proliferation during inflammation via integrin-linked kinase, B-Raf, and ERK1/2-dependent signaling in articular chondrocytes"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Mechanical signals control SOX-9, VEGF, and c-Myc expression and cell proliferation during inflammation via integrin-linked kinase, B-Raf, and ERK1/2-dependent signaling in articular chondrocytes. | Perera et al. Arthritis Research Therapy 2010 12 R106 http content 12 3 R106 RESEARCH ARTICLE Open Access Mechanical signals control SOX-9 VEGF and c-Myc expression and cell proliferation during inflammation via integrin-linked kinase B-Raf and ERK1 2-dependent signaling in articular chondrocytes Priyangi M Perera 1 Ewa Wypasek1 Shashi Madhavan1 Birgit Rath-Deschner2 Jie Liu1 Jin Nam1 Bjoern Rath3 Yan Huang1 James Deschner4 Nicholas Piesco5 Chuanyue Wu6 and Sudha Agarwal 1 Abstract Introduction The importance of mechanical signals in normal and inflamed cartilage is well established. Chondrocytes respond to changes in the levels of proinflammatory cytokines and mechanical signals during inflammation. Cytokines like interleukin IL -1p suppress homeostatic mechanisms and inhibit cartilage repair and cell proliferation. However matrix synthesis and chondrocyte AC proliferation are upregulated by the physiological levels of mechanical forces. In this study we investigated intracellular mechanisms underlying reparative actions of mechanical signals during inflammation. Methods ACs isolated from articular cartilage were exposed to low physiologic levels of dynamic strain in the presence of IL-1p. The cell extracts were probed for differential activation inhibition of the extracellular signal-regulated kinase 1 2 ERK1 2 signaling cascade. The regulation of gene transcription was examined by real-time polymerase chain reaction. Results Mechanoactivation but not IL-1p treatment of ACs initiated integrin-linked kinase activation. Mechanical signals induced activation and subsequent C-Raf-mediated activation of MAP kinases MEK1 2 . However IL-1 p activated B-Raf kinase activity. Dynamic strain did not induce B-Raf activation but instead inhibited IL-1 p-induced B-Raf activation. Both mechanical signals and IL-1 p induced ERK1 2 phosphorylation but discrete gene expression. ERK1 2 activation by mechanical forces induced SRY-related protein-9 SOX-9 .

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