The data were quantified and represented in the form of bar graph

l tissue. Neutrophils, lymphocytes, macrophages, and synovial fibroblasts all significantly increased between the naive and AIA groups, and the AIA plus Ya-s11 group demonstrated a significant decrease in the number of neutrophils, lymphocytes, and BAY41-2272 web macrophages as well as inhibition of synovial fibroblast 2449244 proliferation. No significant change was found in the AIA plus Ya-s11 group compared with the 10725256 AIA group. Effect of Ya-s11 on cathepsin K, MMP-9, TRAP, and TNF-a in AIA Effect of Ya-s11 in Adjuvant-Induced Arthritis subchondral bone marrow but not cartilage. The AIA plus Ya-s11 group demonstrated reduced cathepsin K immunoreactivity in subchondral bone marrow without Effect of Ya-s11 in Adjuvant-Induced Arthritis 7 Effect of Ya-s11 in Adjuvant-Induced Arthritis Ya-s11 , and AIA plus Ya-s11 groups. In the AIA group, MMP-9 immunoreactivity appeared to increase in the ankle joint. Administration of 9 mg/kg but not 3 mg/kg Ya-s11 inhibited AIA-induced MMP-9 expression in the ankle joint. Higher-magnification images of MMP-9 immunoreactivity in the synovial tissue and cartilage with subchondral bone in the naive, AIA, AIA plus Ya-s11 , and AIA plus Ya-s11 groups are taken from Discussion This study employed LPS-induced RAW264.7 murine macrophage cells and AIA as in vitro and in vivo models, respectively, to assess the anti-inflammatory and anti-arthritic effects of Ya-s11. Marine-derived Ya-s11 significantly down-regulated expression of the proinflammatory proteins iNOS and COX-2 in LPS-induced RAW 264.7 murine macrophage cells. Administration of Ya-s11 also significantly inhibited AIA-induced paw edema and the upregulation of arthritis score in a dose-dependent manner. Histopathological and immunohistochemical examination further demonstrated that AIA-induced histological features in the ankle joint and the osteoclast-related proteins, cathepsin K, MMP-9, TRAP, and TNF-awere upregulated in ankle joint tissue in the AIA group. Systemic injection of Ya-s11 not only attenuated AIA-induced pathological changes in the ankle joint, but also significantly reduced the osteoclast-related protein expression. Effect of Ya-s11 anti-inflammatory activity in vitro and in vivo RA is a synovial inflammatory disease characterized by proliferative synovial fibroblasts and infiltrating cells. Previous studies have highlighted the important role played by macrophages in the process of RA. Macrophages mediate synovial inflammation in RA by forming complex cytokine networks with neutrophils, lymphocytes, and synovial fibroblasts and are also critical to osteoclast differentiation. Yas11 was able to downregulate iNOS and COX-2 protein expression in LPS-stimulated macrophage RAW 264.7 cells, a well-established in vitro model for assessing the antiinflammatory activity of compounds. In the in vivo study, AIA rats demonstrated a significantly increased number of macrophages in 8 Effect of Ya-s11 in Adjuvant-Induced Arthritis ankle joint synovial tissue as well as AIA-induced increased of neutrophils and lymphocytes with fibroblast proliferation. Although subcutaneous injection of 3 mg/ml Ya-s11 did not significantly decrease the number of infiltrating cells in synovial tissue, synovial hyperplasia was reduced in this treatment group. Treatment with 9 mg/ml Ya-s11 inhibited synovial inflammation with reduced cell infiltration in AIA-rats. AIA-induced joint destruction with osteoclast-related protein expression Many studies have clearly illustrated the mediation of joi