s/14/S1 Webpage 42 of 54 Figure 1. CD81 belomgs to a family members of cell surface protein that has four transmembrane domains and two outer membrane PDK 1 Signaling loops. Beneath the DNA chip assessment, we found several genes really expressed in rheumatoid arthritis synoviocytes evaluating using the expression in OA or standard synoviocytes. Amongst these genes, tetraspanin CD81 was proven to get involved inside the progression of RA by means of the promotion of Synoviolin expression. Synoviolin is presently often known as a single from the critical progressive factors of RA in synoviocytes. We also showed Synoviolin and CD81 very distributed in RA tissues. The therapeutic influence of modest interfering RNA targeting CD81 was examined by in vivo electroporation approach. Treatment with siCD81 significantly ameliorated paw swelling of collagen induced arthritic rats.

In histological examination, hypertrophy of synovium, bone erosion, and degeneration of articular cartilage were minder in rats treated with siCD81 than within the management group as well as non unique siRNA group. Expression of synoviolin, a rheumatoid regulator, was also suppressed by siCD81. These final results showed that siCD81 would develop into helpful tools for treatment of RA. Additionally, cyclic peptide siCD81 reduced the quantity of CD81 in synovial fluid indicating that quantitative assessment of CD81 opens up the novel and hugely sensitive diagnosis for RA. Reference 1. Nakagawa Shuji, Arai Yuji, Mori Hiroki, Matsushita Yumi, Kubo Toshikazu, Nakanishi Tohru: Small interfering RNA targeting CD81 ameliorated arthritis in rats. Biochem Biophys Res Commun 2009, 388:467 472.

P53 The crucial function of osteocyte derived RANKL in bone homeostasis Tomoki Nakashima1,2, Mikihito Hayashi1,2, Hiroshi Takayanagi1,2 1Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Healthcare and Dental University, Ribonucleic acid (RNA) Yushima 1 5 45, Tokyo, Japan, 2Japan Science and Engineering Agency, ERATO, Takayanagi Osteonetwork Task, Yushima 1 5 45, Tokyo, Japan Arthritis Study & Therapy 2012, 14 53 Receptor activator of NF B ligand, a TNF family molecule, and its receptor RANK are key regulators of osteoclast differentiation and function. Aberrant expression of RANKL explains why autoimmune diseases, cancers, leukemia and periodontal disease result in systemic and local bone loss. In particular, RANKL is the pathogenic factor that cause bone and cartilage destruction in arthritis.

Inhibition of RANKL function by the natural decoy receptor osteoprotegerin or anti RANKL antibody prevents bone loss in postmenopausal osteoporosis, cancer metastases and arthritis. RANKL also regulates T cell/dendritic cell communications, dendritic cell survival and lymph node organogenesis. Intriguingly, RANKL and RANK play an essential part within the maturation of mammary glands in pregnancy buy Torin 2 and lactation.