tailieunhanh - Báo cáo y học: " Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursor"

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: Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors. | Adamopoulos et al. Arthritis Research Therapy 2010 12 R29 http content 12 1 R29 RESEARCH ARTICLE Open Access Interleukin-17A upregulates receptor activator of NF-kB on osteoclast precursors Iannis E Adamopoulos 1 Cheng-chi Chao1 Richard Geissler2 Drake Laface1 Wendy Blumenschein1 Yoichiro Iwakura3 Terrill McClanahan1 and Edward P Bowman 1 Abstract Introduction The interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis. Methods Human CD14 cells were isolated from healthy donors cultured on dentine slices and coverslips and stimulated with IL-17A and or receptor activator of NF-kB ligand RANKL . Osteoclast differentiation was evaluated by gene expression flow cytometry tartrate-resistant acid phosphatase staining fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type Wt and IL-17A- - mice using micro-computer tomography and serum RANKL osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A- - and Wt mice. Results IL-17A upregulates the receptor activator for NF-kB receptor on human osteoclast precursors in vitro leading to increased sensitivity to RANKL signalling osteoclast differentiation and bone loss. IL-17A- - mice have physiological bone homeostasis indistinguishable from Wt mice and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts. Conclusions Collectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases. Introduction The pathologic outcome of the activated immune system interacting with the skeletal system is evidenced by articular bone erosion and joint loss of function seen in autoimmune joint diseases