Browsing by Author "Diez-Perez, Adolfo"

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    Pro-osteoporotic miR-320a impairs osteoblast function and induces oxidative stress
    (PLOS, 2018-11-28) De-Ugarte, Laura; Balcells, Susana; Nogues, Xavier; Grinberg, Daniel; Diez-Perez, Adolfo; Garcia-Giralt, Natalia; Anatomy and Cell Biology, IU School of Medicine
    MicroRNAs (miRNAs) are important regulators of many cellular processes, including the differentiation and activity of osteoblasts, and therefore, of bone turnover. MiR-320a is overexpressed in osteoporotic bone tissue but its role in osteoblast function is unknown. In the present study, functional assays were performed with the aim to elucidate the mechanism of miR-320a action in osteoblastic cells. MiR-320a was either overexpressed or inhibited in human primary osteoblasts (hOB) and gene expression changes were evaluated through microarray analysis. In addition, the effect of miR-320a on cell proliferation, viability, and oxidative stress in hOB was evaluated. Finally, matrix mineralization and alkaline phosphatase activity were assessed in order to evaluate osteoblast functionality. Microarray results showed miR-320a regulation of a number of key osteoblast genes and of genes involved in oxidative stress. Regulation of osteoblast differentiation and ossification appeared as the best significant biological processes (PANTHER P value = 3.74E-05; and P value = 3.06E-04, respectively). The other enriched pathway was that of the cellular response to cadmium and zinc ions, mostly by the overexpression of metallothioneins. In hOBs, overexpression of miR-320a increased cell proliferation and oxidative stress levels whereas mineralization capacity was reduced. In conclusion, overexpression of miR-320a increased stress oxidation levels and was associated with reduced osteoblast differentiation and functionality, which could trigger an osteoporotic phenotype.
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    The tissue diagnostic instrument
    (2009-05) Hansma, Paul; Yu, Hongmei; Schultz, David; Rodriguez, Azucena; Yurtsev, Eugene A.; Orr, Jessica; Tang, Simon; Miller, Jon; Wallace, Joseph M.; Zok, Frank; Li, Cheng; Souza, Richard; Proctor, Alexander; Brimer, Davis; Nogues-Solan, Xavier; Mellbovsky, Leonardo; Peña, M Jesus; Diez-Ferrer, Oriol; Mathews, Phillip; Randall, Connor; Kuo, Alfred; Chen, Carol; Peters, Mathilde; Kohn, David; Buckley, Jenni; Li, Xiaojuan; Pruitt, Lisa; Diez-Perez, Adolfo; Alliston, Tamara; Weaver, Valerie; Lotz, Jeffrey
    Tissuemechanical properties reflect extracellular matrix composition and organization, and as such, their changes can be a signature of disease. Examples of such diseases include intervertebral disk degeneration, cancer, atherosclerosis, osteoarthritis, osteoporosis, and tooth decay. Here we introduce the tissue diagnostic instrument (TDI), a device designed to probe the mechanical properties of normal and diseased soft and hard tissues not only in the laboratory but also in patients. The TDI can distinguish between the nucleus and the annulus of spinal disks, between young and degenerated cartilage, and between normal and cancerous mammary glands. It can quantify the elastic modulus and hardness of the wet dentin left in a cavity after excavation. It can perform an indentation test of bone tissue, quantifying the indentation depth increase and other mechanical parameters. With local anesthesia and disposable, sterile, probe assemblies, there has been neither pain nor complications in tests on patients. We anticipate that this unique device will facilitate research on many tissue systems in living organisms, including plants, leading to new insights into disease mechanisms and methods for their early detection.