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In this paper, a bulk Mg–Zn–Y alloy reinforced by quasicrystalline particles was produced by hot extrusion of rapidly-solidified powders. MgZn 4.3 Y 0.7 powders with different particle sizes were prepared by an inert gas atomizer and then extruded at 380 °C with extrusion ratios of 10:1, 15:1, and 20:1. Microstructural studies were performed using an optical microscope, scanning electron microscope, transmission electron microscope, and X-ray diffraction. The mechanical strength and hardness of the extruded materials were enhanced by employing finer Mg alloy powders. More uniform deformation of powders in extruded billets with good tensile properties was achieved at higher extrusion ratios, especially for finer powders. The high strength of the MgZn 4.3 Y 0.7 alloy was preserved at elevated temperatures due to the presence of icosahedral phase nanoparticles.

Background Carbon monoxide (CO) and nitric oxide (NO) each have unique roles for various inflammatory states, including inflammatory bone resorption. Although it is known that NO can induce the expression of the cytoprotective enzyme HO-1, there is no information as to whether the protective effect of CO requires NO production or whether CO must induce the expression of HO-1 to exert its functional effects. Methods Murine osteoblast cells, MC3T3E1 osteoblasts, were cultured for CO and NO-associated HO-1 experiments and were transfected with pcDNA 3, pcDNA 3-HO-1, control siRNA or HO-1 siRNA using Nucleofector. For cell death measurement, MTT and annexin V assays were used. We performed Western blotting to check the expressions of HO-1 and iNOs and measured the HO-1 enzyme activity. We also measured the amounts of nitrite and nitrate using Griess reagents. Results The increased expression of HO-1 is required for the protective effect of NO and a single treatment of CO can increase the expression of HO-1, and this is also important for the protective effect of CO in MC3T3E1 osteoblasts. CO as well as NO attenuates the TNF-α-induced apoptosis in osteoblasts. The anti-apoptotic effect of CO or NO is not mediated by cGMP, and CO has no effect on the release of NO. The inhibition of HO-1 with using the HO-1 inhibitor ZnPP or HO-1 siRNA resulted in a striking increase of apoptosis in the CO/TNF-α-treated cells. Furthermore, HO-1 overexpression showed resistance against the TNF-α-induced cytotoxicity in the MC3T3E1 osteoblasts. Conclusions There is a need for HO-1 expression to mediate the protection provided by exogenous CO or NO in osteoblasts.

The toxicity of thapsigargin, a selective inhibitor of endoplasmic reticular Ca 2+ -ATPase, was investigated in osteoblasts. We induced apoptosis in murine osteoblastic MC3T3E1 cells by exposure to the thapsigargin. Thapsigargin transiently increased the phosphotransferase activity of c-Jun N-terminal kinases1 (JNK1), which might in turn activate transcriptional activity of activation protein-1 (AP-1). We then prepared extracts from thapsigargin-treated MC3T3E1 cells and monitored cleavage of acetyl-YVAD-AMC and acetyl-DEVD-AMC, fluorogenic substrates for caspase 1-like and caspase 3-like proteases, respectively. Thapsigargin significantly increased the proteolytic activity of caspase 3-like proteases, but not the activity of caspase 1-like proteases. Furthermore, thapsigargin increased the transcriptional activity of nuclear factor-κB (NF-κB). These data suggest that thapsigargin-induced apoptosis in osteoblasts may be via activation of JNK1, caspase 3-like family proteases, and transcriptional factors including AP-1 and NF-κB.

Background Clustered occurrences of ankylosing spondylitis (AS) in the family have been noticed. Few phenotype studies on familial AS suggest the distinct features of the disease compared to sporadic disease. Objectives The aim of this study is to investigate clinical characteristics and incidence of familial form of AS compared to sporadic AS. Methods We evaluated patients with AS confirmed by the modified New York criteria for familial history of AS (one or more first to third degrees relatives). The clinical characteristics and the recurrence risks (number of AS patients/number of familial members) of the familial AS compared to sporadic AS were investigated. Results Out of a total of 204 AS patients (165 males, 39 females, mean age 37.0±13.1 years), 38 patients (18.6%) reported that they had a familial history of AS. The recurrence risks in the familial AS patients for first, second and third degree family members were 14.5%, 5.2%, and 4.4% respectively. ESR (22.6±22.2 vs. 35.4±34.4, p=0.029) and CRP (1.24±1.7 vs. 2.43±3.3, p=0.003) at diagnosis, body mass index (21.9±2.7 vs. 23.7±3.3, p=0.002) and frequency of oligoarthritis (13.2% vs. 33.7%, p=0.021) were significantly lower in the familial form. The presence of HLA-B27 (97.4% vs. 83.1%, p=0.044) was significantly higher in familial AS. ![Figure][1] Conclusions We report that Korean AS patients with a familial history had a higher presence of HLA-B27 than sporadic AS. The recurrence risk in the familial AS was highest in first degree relatives, indicating higher susceptibility to the disease. Distinct phenotypes of familial AS were lower frequency of oligoarthritis, lower ESR and CRP at diagnosis and lower body mass index. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3469 [1]: pending:yes

The induction of interleukin-6 (IL-6), using a proinflammatory cytokine (tumor necrosis factor-alpha), was studied in a human osteoblast cell line (MG-63) in relation to p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB transcription factor. When added to MG-63 cells, tumor necrosis factor-alpha (TNF-alpha) had a stimulatory effect on the production of IL-6, and this elevation was significantly reduced by SB203580, a specific p38 MAPK inhibitor. In addition, the stimulation of IL-6 release was also reduced by pyrrolidine dithiocarbamate (PDTC) or NF-kappaB SN50, which has been reported to be a potent NF-kappaB inhibitor. Both the NF-kappaB inhibitors in the presence of SB203580 had a more inhibitory effect on IL-6 release. In this study, TNF-alpha stimulated NF-kappaB binding affinity as well as p38 MAP kinase activation, leading to the release of IL-6. However, the specific inhibitor of p38 MAPK, SB203580, had no effect on TNF-alpha-induced NF-kappaB activation and both NF-kappaB inhibitors failed to reduce the p38 MAPK activation in the TNF-alpha-stimulated osteoblasts. In addition, inhibition of p38 MAPK partially, but significantly, impaired TNF-alpha-regulated release of osteocalcin, an important differentiation marker in osteoblasts. These results strongly suggest that both p38 MAPK and NF-kappaB are required in TNF-alpha-induced IL-6 synthesis and that these two TNF-alpha-activated pathways can be primarily dissociated. Furthermore, p38 MAPK may play a significant role in differentiation in MG-63 cells.