It can be hence suggested ROCK inhibitors that the SNP algorithms can predict responders and adverse occasions just before the initiation of treatment with abatacept. Conclusions: These highly accurate algorithms working with SNP examination may be helpful from the prediction of responsiveness and adverse activities prior to therapy with abatacept, and in this way can contribute to potential tailor manufactured treatment method with biologic agents.

P49 Servicing of mitochondrial DNA copy range is important for osteoclast survival Tsuyoshi Miyazaki1, Shuuichi Mori1, Kazuhiro Shigemoto1, Nils Goran Larsson2, Takeshi Nakamura3, Shigekaki Kato3, Syk inhibitors in development Tomoki Nakashima4, Hiroshi Takayanagi4, Sakae Tanaka5 1Department of Geriatric Medication, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo 173 0015, Japan, 2Division of Metabolic Disorders, Karolinska Institute, Stockholm, Sweden, 3Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113 0032, Japan, 4Department of Cell Signaling, Graduate School of Health-related and Dental Sciences, Tokyo Health-related and Dental University, Tokyo 113 8549, Japan, 5Department of Orthopaedic Surgical treatment, Faculty of Medication, The University of Tokyo, Tokyo 113 0033, Japan Arthritis Exploration & Therapy 2012, 14 49 Background: There is accumulating evidence that osteoclasts, the primary cells responsible for bone resorption, are involved in bone and joint destruction in rheumatoid arthritis. Bone resorption is really regulated by mature osteoclast function as well as osteoclastogenesis.

The life span of mature osteoclasts is relatively short both in vitro and in vivo, and once differentiated, they rapidly die in the absence of supporting cell or growth factors. Mitochondria is known as Plastid powerhouse of cell because they generate most of the cells supply of adenosine triphosphate, used as a source of chemical energy. In addition to supplying cellular energy, mitochondria are involved in a range of other processes, such as signaling, cellular differentiation, cell growth, and cell death. Transcription and replication of mitochondrial DNA are important steps in mitochondrial biogenesis and mitochondrial transcription factor A is important for mtDNA transcription and replication. However, the functional significance of mitochondria has not been established in osteoclastic bone resorption.

Materials and methods: To address this question, STAT3 inhibitors in clinical trials we generated osteoclast specific Tfam conditional knock out mice by mating Tfamfl/fl mice with cathepsin K Cre transgenic mice, in which the Cre recombinase gene is knocked into the cathepsin K locus and specifically expressed in mature osteoclasts. The in vivo effects of Tfam deficiency on bone metabolism were examined by histological and histomorphometric evaluation. The survival and bone resorbing activity of Tfam cKO osteoclasts were determined by in vitro survival assay and pit formation assay, respectively. Results: The expression level of Tfam, mtDNA copy quantity, and cellular ATP level were markedly reduced in osteoclasts derived from Tfam cKO mice. The body size of Tfam cKO mice was smaller than that of the control mice, although trabecular bone volume remained unchanged by Tfam deficiency.