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Nitric oxide (NO) plays a crucial role in the physiological and pathophysiological regulations of osteoblast functions. This study is designed to evaluate the toxic effects of NO released by sodium nitroprusside (SNP), an NO donor, on neonatal Wistar rat calvarial osteoblasts from the analyses of cell viability, alkaline phosphatase (ALP) activity, cell morphology, apoptotic cells, terminal deoxynucleotidyl transferase-mediated dUTP nick end-label (TUNEL) assay, DNA ladder, and immunocytochemistry and Western blot for proapoptotic Bax protein. SNP increased the levels of nitrite, an oxidative product of NO, in the culture medium of osteoblasts in concentration-and time-dependent manners, and altered cell morphologies to round and shrinkage shapes. Administration of osteoblasts with SNP resulted in concentration-and time-dependent decreases of cell viability and ALP activity. Analysis of apoptotic cells revealed that SNP increased the percentages of osteoblasts processing apoptosis. Analyses of TUNEL and DNA ladder showed that SNP caused DNA fragmentation. Pretreatment with cycloheximide, an inhibitor of protein synthesis, partially blocked SNP-induced osteoblast apoptosis. Imunocytochemical and immunoblotting analyses revealed that SN P increased Bax protein in osteoblasts. This study suggests that SNP could increase the levels of NO in osteoblasts, and cause osteoblast

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This in vivo pilot study explored the use of mesenchymal stem cell (MSC) containing tissue engineering constructs in repair of osteochondral defects. Osteochondral defects were created in the medial condyles of both knees of 16 miniature pigs. One joint received a cell/collagen tissue engineering construct with or without pretreatment with transforming growth factor b (TGF-b) and the other joint from the same pig received no treatment or the gel scaffold only. Six months after surgery, in knees with no treatment, all defects showed contracted craters; in those treated with the gel scaffold alone, six showed a smooth gross surface, one a hypertrophic surface, and one a contracted crater; in those with undifferentiated MSCs, five defects had smooth, fully repaired surfaces or partially repaired surfaces, and one defect poor repair; in those with TGF-b-induced differentiated MSCs, seven defects had smooth, fully repaired surfaces or partially repaired surfaces, and three defects showed poor repair. In Pineda score grading, the group with undifferentiated MSC, but not the group with TGF-b-induced differentiated MSCs, had significantly lower subchondral, cell morphology, and total scores than the groups with no or gel-only treatment. The compressive stiffness was larger in cartilage without surgical treatment than the treated area within each group. In conclusion, this preliminary pilot study suggests that using undifferentiated MSCs might be a better approach than using TGF-b-induced differentiated MSCs for in vivo tissue engineered treatment of osteochondral defects. ß

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Objective. To examine the role of sirtuin-1 (SIRT-1)/FoxO3a in the expression of cysteine-rich protein 61 (CYR-61) in rheumatoid arthritis synovial fibroblasts (RASFs) and the influence of simvastatin on this pathway, and to determine the relationship between disease progression and FoxO3a/CYR-61 signaling in synovial fibroblasts in vivo using a rat model of collagen-induced arthritis (CIA).Methods. In RASFs, the expression of CYR-61 and SIRT-1, the localization of FoxO3a in the nucleus/ cytoplasm, and the phosphorylation/acetylation of FoxO3a were examined by Western blotting. Secretion of CCL20 was assessed by enzyme-linked immunosorbent assay. Promoter activity of the Cyr61 gene was evaluated by luciferase assay, with or without forced expression of FoxO3a and SIRT-1 by lentiviral transduction. FoxO3a-Cyr61 promoter interaction was examined by chromatin immunoprecipitation. In rats with CIA, the expression of CYR-61 and phosphorylated FoxO3a in synovial fibroblasts was examined by immunohistochemistry.Results. In RASFs, simvastatin suppressed the tumor necrosis factor ␣ (TNF␣)-induced production of CYR-61 and CCL20. Nuclear levels of FoxO3a were

Cross‐sectional geometrical (CSG) properties of an Iron Age Samnite group from the Alfedena necropolis (Abruzzo, Italy, 2600–2400 B.P.) are compared with a Ligurian Neolithic sample (6000–5500 B.P.). In the period under examination, Samnites were organized in a tribal confederation led by patrilinear aristocracies, indicating incipient social stratification. In comparison, Neolithic society lacked clear signs of social hierarchy. The subsistence of both groups was mainly based on pastoralism and agriculture, but changes in habitual behavior are expected due to the socio‐economic transformations that characterized the Iron Age. The Samnites' warlike ideology suggests that unimanual weapon‐use and training would have become frequent for males. The intensification of agriculture and the adoption of transhumant pastoralism, performed by a smaller subset of the population, likely led to a lower average level of logistic mobility. The strongly genderized ideology of the period suggests a strict sexual division of labor, with women primarily performing sedentary tasks. CSG properties based on periosteal contours were calculated for humeri, femora, and tibiae (N = 61). Results corroborated the expectations: Alfedena males show substantial humeral bilateral asymmetry, indicating prevalent use of one arm, likely due to weapon training. In both sexes lower limb results indicate reduced mobility with respect to the Neolithic group. Sexual dimorphism is significant in both humeral asymmetry and lower limb indicators of mobility. Although both groups could be broadly defined as agropastoral based on archeological and historical evidence, CSG analysis confirmed important differences in habitual behavior. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.