Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 14Lamin A/C Is Dispensable To Mechanical Repression of Adipogenesis(MDPI, 2021) Goelzer, Matthew; Dudakovic, Amel; Özçivici, Engin; Sen, Buer; Özçivici, Engin; Rubin, Janet; van Wijnen, Andre J.; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyMesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein vital to the nuclear architecture that supports chromatin organization and differentiation and contributes to the mechanical integrity of the nucleus. We investigated whether lamin A/C and mechanoresponsiveness are functionally coupled during adipogenesis in MSCs. siRNA depletion of lamin A/C increased the nuclear area, height, and volume and decreased the circularity and stiffness. Lamin A/C depletion significantly decreased markers of adipogenesis (adiponectin, cellular lipid content) as did LIV treatment despite depletion of lamin A/C. Phosphorylation of focal adhesions in response to mechanical challenge was also preserved during loss of lamin A/C. RNA-seq showed no major adipogenic transcriptome changes resulting from LIV treatment, suggesting that LIV regulation of adipogenesis may not occur at the transcriptional level. We observed that during both lamin A/C depletion and LIV, interferon signaling was downregulated, suggesting potentially shared regulatory mechanism elements that could regulate protein translation. We conclude that the mechanoregulation of adipogenesis and the mechanical activation of focal adhesions function independently from those of lamin A/C.Article Citation - WoS: 5Citation - Scopus: 5Low Magnitude High Frequency Vibrations Expedite the Osteogenesis of Bone Marrow Stem Cells on Paper Based 3d Scaffolds(Springer, 2020) Özçivici, Engin; Meşe Özçivici, Gülistan; Özçivici, Engin; 03.01. Department of Bioengineering; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of TechnologyAnabolic effects of low magnitude high frequency (LMHF) vibrations on bone tissue were consistently shown in the literature in vivo, however in vitro efforts to elucidate underlying mechanisms are generally limited to 2D cell culture studies. Three dimensional cell culture platforms better mimic the natural microenvironment and biological processes usually differ in 3D compared to 2D culture. In this study, we used laboratory grade filter paper as a scaffold material for studying the effects of LHMF vibrations on osteogenesis of bone marrow mesenchymal stem cells in a 3D system. LMHF vibrations were applied 15 min/day at 0.1 g acceleration and 90 Hz frequency for 21 days to residing cells under quiescent and osteogenic conditions. mRNA expression analysis was performed for alkaline phosphatase (ALP) and osteocalcin (OCN) genes, Alizarin red S staining was performed for mineral nodule formation and infrared spectroscopy was performed for determination of extracellular matrix composition. The highest osteocalcin expression, mineral nodule formation and the phosphate bands arising from the inorganic phase was observed for the cells incubated in osteogenic induction medium with vibration. Our results showed that filter paper can be used as a model scaffold system for studying the effects of mechanical loads on cells, and LMHF vibrations induced the osteogenic differentiation of stem cells.Article Citation - WoS: 28Citation - Scopus: 30Bone Marrow Stem Cells Adapt To Low-Magnitude Vibrations by Altering Their Cytoskeleton During Quiescence and Osteogenesis(TUBITAK, 2015) Demiray, Levent; Özçivici, Engin; Özçivici, Engin; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyApplication of mechanical vibrations is anabolic to bone tissue, not only by guiding mature bone cells to increased formation, but also by increasing the osteogenic commitment of progenitor cells. However, the sensitivity and adaptive response of bone marrow stem cells to this loading regimen has not yet been identified. In this study, we subjected mouse bone marrow stem cell line D1-ORL-UVA to daily mechanical vibrations (0.15 g, 90 Hz, 15 min/day) for 7 days, both during quiescence and osteogenic commitment, to identify corresponding ultrastructural adaptations on cellular and molecular levels. During quiescence, mechanical vibrations significantly increased total actin content and actin fiber thickness, as measured by phalloidin staining and fluorescent microscopy. Cellular height also increased, as measured by atomic force microscopy, along with the expression of focal adhesion kinase (PTK2) mRNA levels. During osteogenesis, mechanical vibrations increased the total actin content, actin fiber thickness, and cytoplasmic membrane roughness, with significant increase in Runx2 mRNA levels. These results show that bone marrow stem cells demonstrate similar cytoskeletal adaptations to low-magnitude high-frequency mechanical loads both during quiescence and osteogenesis, potentially becoming more sensitive to additional loads by increased structural stiffness.Article Citation - WoS: 25Citation - Scopus: 27Osteogenic Differentiation of Mesenchymal Stem Cells on Random and Aligned Pan/Ppy Nanofibrous Scaffolds(SAGE Publications, 2019) Meşe Özçivici, Gülistan; Selamet, Yusuf; Baskan, Öznur; Özçivici, Engin; Yılmaz, Selahattin; Özçivici, Engin; 03.01. Department of Bioengineering; 03.02. Department of Chemical Engineering; 01. Izmir Institute of Technology; 04.03. Department of Molecular Biology and Genetics; 04.05. Department of Pyhsics; 03. Faculty of Engineering; 04. Faculty of ScienceThe aim of this study was to develop random and aligned polyacrilonitrile (PAN)/polypyrrole (PPy) nanofibrous scaffolds by electrospinning technique for osteogenic differentiation of mesenchymal stem cells. Nanofibers were fabricated successfully as straight, smooth, and free from bead formation. The average diameter of random and aligned nanofibers was 268(+/- 49) nm and 225(+/- 72) nm, respectively. Alignment process increased the tensile strength of nanofibers 3.9-fold, while the tensile strain of nanofibers decreased by 78%. PAN/PPy nanofibers were hydrophilic with the contact angle value of about 32 degrees and alignment did not affect the contact angle value. Random and aligned PAN/PPy nanofibers were investigated as a scaffold material for osteogenic differentiation of D1 ORL UVA mouse bone marrow mesenchymal stem cells. Cells were able to attach and grow on nanofibers confirmed by cell viability results. Stem cells that were cultured with osteogenic induction were able to mineralize on electrospun nanofibers based on alizarin red and Von Kossa dye staining. For aligned PPy nanofibers, mineralization occurred in the fiber alignment direction. Consequently, PAN/PPy nanofibrous mats in both random and aligned forms would be potential candidates for bone tissue engineering.Article Citation - WoS: 8Citation - Scopus: 11Application of Low Intensity Mechanical Vibrations for Bone Tissue Maintenance and Regeneration(TÜBİTAK, 2016) Ölçüm, Melis; Özçivici, Engin; Baskan, Öznur; Baskan, Öznur; Karadaş, Özge; Özçivici, Engin; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringPhysical exercise is beneficial for bone tissue health, yet its usage is limited for preventing osteoporosis. Even though natural for the bone tissue from development to homeostasis, mechanical loads present with a multitude of physical parameters, including amplitude, duration, frequency, and distribution. Utilizing the most beneficial parameters of mechanical loads may potentiate a nonpharmaceutical tool for biotechnology to prevent and treat bone loss related to aging, bedrest, sedentary lifestyles, weightlessness, and other diseases. Low intensity vibrations (LIVs) consist of mechanical loads with amplitudes smaller than loads prescribed by habitual activity, with a higher frequency. In this review, literature covering LIV signal application on bone tissue and cellular and molecular level is presented. Studies indicate that LIV signals are safe, anabolic, and anticatabolic for skeletal tissue and are of great significance in regenerative medicine applications.Article Citation - WoS: 26Citation - Scopus: 32Low-Intensity Vibrations Normalize Adipogenesis-Induced Morphological and Molecular Changes of Adult Mesenchymal Stem Cells(SAGE Publications Inc., 2017) Baskan, Öznur; Özçivici, Engin; Meşe Özçivici, Gülistan; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 04.03. Department of Molecular Biology and Genetics; 03. Faculty of Engineering; 04. Faculty of ScienceBone marrow mesenchymal stem cells that are committed to adipogenesis were exposed daily to high-frequency low-intensity mechanical vibrations to understand molecular, morphological and ultrastructural adaptations to mechanical signals during adipogenesis. D1-ORL-UVA mouse bone marrow mesenchymal stem cells were cultured with either growth or adipogenic medium for 1 week. Low-intensity vibration signals (15 min/day, 90 Hz, 0.1 g) were applied to one group of adipogenic cells, while the other adipogenic group served as a sham control. Cellular viability, lipid accumulation, ultrastructure and morphology were determined with MTT, Oil-Red-O staining, phalloidin staining and atomic force microscopy. Semiquantitative reverse transcription polymerase chain reaction showed expression profile of the genes responsible for adipogenesis and ultrastructure of cells. Low-intensity vibration signals increased viability of the cells in adipogenic culture that was reduced significantly compared to quiescent controls. Low-intensity vibration signals also normalized the effects of adipogenic condition on cell morphology, including area, perimeter, circularization and actin cytoskeleton. Furthermore, low-intensity vibration signals reduced the expression of some adipogenic markers significantly. Mesenchymal stem cells are sensitive and responsive to mechanical loads, but debilitating conditions such as aging or obesity may steer mesenchymal stem cells toward adipogenesis. Here, daily application of low-intensity vibration signals partially neutralized the effects of adipogenic induction on mesenchymal stem cells, suggesting that these signals may provide an alternative and/or complementary option to reduce fat deposition.