s/14/S1 Webpage 42 of 54 Figure 1. CD81 belomgs to a household of cell surface protein which has 4 transmembrane domains and two outer membrane TGF-beta loops. Beneath the DNA chip evaluation, we discovered various genes highly expressed in rheumatoid arthritis synoviocytes evaluating using the expression in OA or typical synoviocytes. Amid these genes, tetraspanin CD81 was proven to be concerned inside the progression of RA by way of the promotion of Synoviolin expression. Synoviolin is already often known as a single on the essential progressive aspects of RA in synoviocytes. We also showed Synoviolin and CD81 really distributed in RA tissues. The therapeutic result of modest interfering RNA targeting CD81 was examined by in vivo electroporation technique. Therapy with siCD81 substantially ameliorated paw swelling of collagen induced arthritic rats.

In histological examination, hypertrophy of synovium, bone erosion, and degeneration of articular cartilage had been minder in rats handled with siCD81 than during the control group and also the non precise siRNA group. Expression of synoviolin, a rheumatoid regulator, was also suppressed by siCD81. These results showed that siCD81 would become efficient equipment for therapy of RA. Additionally, order LY364947 siCD81 diminished the amount of CD81 in synovial fluid indicating that quantitative assessment of CD81 opens up the novel and really sensitive diagnosis for RA. Reference 1. Nakagawa Shuji, Arai Yuji, Mori Hiroki, Matsushita Yumi, Kubo Toshikazu, Nakanishi Tohru: Little interfering RNA targeting CD81 ameliorated arthritis in rats. Biochem Biophys Res Commun 2009, 388:467 472.

P53 The important role of osteocyte derived RANKL in bone homeostasis Tomoki Nakashima1,2, Mikihito Hayashi1,2, Hiroshi Takayanagi1,2 1Department of Cell Signaling, Graduate School of Health-related and Dental Sciences, Tokyo Health-related and Dental University, Metastasis Yushima 1 5 45, Tokyo, Japan, 2Japan Science and Technology Agency, ERATO, Takayanagi Osteonetwork Venture, Yushima 1 5 45, Tokyo, Japan Arthritis Investigate & Therapy 2012, 14 53 Receptor activator of NF B ligand, a TNF household 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 function while in the maturation of mammary glands in pregnancy ROCK2 inhibitor and lactation.