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: 1Citation - Scopus: 1Abnormally Accumulated Gm2 Ganglioside Contributes To Skeletal Deformity in Tay-Sachs Mice(Springer Heidelberg, 2024) Demir, Secil Akyildiz; Seyrantepe, VolkanTay-Sachs Disease is a rare lysosomal storage disorder caused by mutations in the HEXA gene, responsible for the degradation of ganglioside GM2. In addition to progressive neurodegeneration, Tay-Sachs patients display bone anomalies, including kyphosis. Tay-Sachs disease mouse model (Hexa-/-Neu3-/-) shows both neuropathological and clinical abnormalities of the infantile-onset disease phenotype. In this study, we investigated the effects of GM2 accumulation on bone remodeling activity. Here, we evaluated the bone phenotype of 5-month-old Hexa-/-Neu3-/- mice with age-matched control groups using gene expression analysis, bone plasma biomarker analysis, and micro-computed tomography. We demonstrated lower plasma alkaline phosphatase activity and calcium levels with increased tartrate-resistant acid phosphatase levels, indicating reduced bone remodeling activity in mice. Consistently, gene expression analysis confirmed osteoblast reduction and osteoclast induction in the femur of mice. Micro-computed tomography and analysis show reduced trabecular bone volume, mineral density, number, and thickness in Hexa-/-Neu3-/- mice. In conclusion, we demonstrated that abnormal GM2 ganglioside accumulation significantly triggers skeletal abnormality in Tay-Sachs mice. We suggest that further investigation of the molecular basis of bone structure anomalies is necessary to elucidate new therapeutic targets that prevent the progression of bone symptoms and improve the life standards of Tay-Sachs patients.Article Citation - WoS: 46Citation - Scopus: 53Chitosan-Hybrid Poss Nanocomposites for Bone Regeneration: the Effect of Poss Nanocage on Surface, Morphology, Structure and in Vitro Bioactivity(Elsevier, 2020) Tamburacı, Sedef; Tıhmınlıoğlu, FundaPOSS, regarded as the smallest silica particle, is widely used as nanofiller in polymer systems. POSS-based nanocomposites are deduced as novel materials having potency for biomedical applications owing to the enhanced biocompatibility and physicochemical characteristics. The aim of this work was to integrate the beneficial features of chitosan (CS) and OctaTMA-POSS nanoparticle to design nanocomposite for bone tissue regeneration. The nanocomposite scaffolds were fabricated by freeze-drying. The effects of POSS incorporation on morphology and structure of CS matrix were examined. Bioactivity and osteogenic effects of the POSS nanoparticles were investigated with cytocompatibility, cell proliferation, alkaline phosphatase activity, osteocalcin production and biomineralization assays. PUSS incorporation altered the surface morphology by increasing surface roughness. Nanocomposite scaffolds with 82-90% porosity exhibited an increase in compression modulus of scaffolds (78-107 kPa) compared to control CS group (56 kPa). Results indicated that CS-POSS scaffolds were found cytocompatible with 3T3, MG-63 and Saos-2 cell lines. POSS incorporation showed promising effects on osteoblast adhesion and proliferation as well as increasing ALP activity, octeocalcin secretion and biomineralization of cells. (C) 2019 Elsevier B.V. All rights reserved.Article Citation - WoS: 51Citation - Scopus: 60Biosilica Incorporated 3d Porous Scaffolds for Bone Tissue Engineering Applications(Elsevier Ltd., 2018) Tamburacı, Sedef; Tıhmınlıoğlu, FundaAs a natural and abundant silica mineral, diatomite particles (SiO2-nH2O) have been used in several areas such as filtration, photonics, sound and heat insulation, filler material and drug delivery due to its abundance, inexpensive cost, unique morphology and porous structure. But up to date, diatomite incorporated silica based scaffolds have not been used for bone tissue engineering applications. In the present study, the goal was to combine the useful biomaterial properties of both chitosan and diatomite as biocomposite organic/inorganic biomaterial for bone tissue engineering applications and optimize the silica content of the composites in order to obtain optimum morphological structure, high mechanical properties, enlarged surface area and enhanced cell proliferation. The effect of silica loading on the mechanical, morphological, chemical, and surface properties, wettability and biocompatibility of composite scaffolds were investigated. In addition, in vitro cytotoxicity and cellular activities including cell proliferation, ALP activity and biomineralization were investigated in order to determine biological activity of the composite scaffolds. Diatomite particles lead to enhancement in the water uptake capacity of scaffolds. Chitosan-silica composites exhibited 82–90% porosity. Wet chitosan-silica composite scaffolds exhibited higher compression moduli when compared to pure chitosan scaffold in the range of 67.3–90.1 kPa. Average pore size range of chitosan-diatomite composite scaffolds was obtained as 218-319 μm. In vitro results indicated that chitosan-diatomite composites did not show any cytotoxic effect on 3T3, MG-63 and Saos-2 cell lines. Scaffolds were found to be favorable for osteoblast proliferation. Diatomite incorporation showed promising effects on enhancing ALP activity as well as mineral formation on scaffold surface. Thus, the prepared scaffolds in this study can be considered prospective material for bone tissue engineering applications.Article Citation - WoS: 62Citation - Scopus: 72Diatomite Reinforced Chitosan Composite Membrane as Potential Scaffold for Guided Bone Regeneration(Elsevier Ltd., 2017) Tamburacı, Sedef; Tıhmınlıoğlu, FundaIn this study, natural silica source, diatomite, incorporated novel chitosan based composite membranes were fabricated and characterized for bone tissue engineering applications as possible bone regeneration membrane. The effect of diatomite loading on the mechanical, morphological, chemical, thermal and surface properties, wettability and in vitro cytotoxicity and cell proliferation on of composite membranes were investigated and observed by tensile test, atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), protein adsorption assay, air/water contact angle analysis and WST-1 respectively. Swelling studies were also performed by water absorption capacity determination. Results showed that incorporation of diatomite to the chitosan matrix increased the surface roughness, swelling capacity and tensile modulus of membranes. An increase of about 52% in Young's modulus was achieved for 10 wt% diatomite composite membranes compared with chitosan membranes. High cell viability results were obtained with indirect extraction method. Besides, in vitro cell proliferation and ALP activity results showed that diatom incorporation significantly increased the ALP activity of Saos-2 cells cultured on chitosan membranes. The novel composite membranes prepared in the present study with tunable properties can be considered as a potential candidate as a scaffold in view of its enhanced physical & chemical properties as well as biological activities for bone tissue engineering applications.Article Citation - WoS: 18Citation - Scopus: 21Genetic Loci That Control the Loss and Regain of Trabecular Bone During Unloading and Reambulation(John Wiley and Sons Inc., 2013) Judex, Stefan; Zhang, Weidong; Donahue, Leah Rae; Özçivici, EnginChanges in trabecular morphology during unloading and reloading are marked by large variations between individuals, implying that there is a strong genetic influence on the magnitude of the response. Here, we subjected more than 350 second-generation (BALBxC3H) 4-month-old adult female mice to 3 weeks of hindlimb unloading followed by 3 weeks of reambulation to identify the quantitative trait loci (QTLs) that define an individual's propensity to either lose trabecular bone when weight bearing is removed or to gain trabecular bone when weight bearing is reintroduced. Longitudinal in vivo micro-computed tomography (μCT) scans demonstrated that individual mice lost between 15% and 71% in trabecular bone volume fraction (BV/TV) in the distal femur during unloading (average: -43%). Changes in trabecular BV/TV during the 3-week reambulation period ranged from a continuation of bone loss (-18%) to large additions (56%) of tissue (average: +10%). During unloading, six QTLs accounted for 21% of the total variability in changes in BV/TV whereas one QTL accounted for 6% of the variability in changes in BV/TV during reambulation. QTLs were also identified for changes in trabecular architecture. Most of the QTLs defining morphologic changes during unloading or reambulation did not overlap with those QTLs identified at baseline, suggesting that these QTLs harbor genes that are specific for sensing changes in the levels of weight bearing. The lack of overlap in QTLs between unloading and reambulation also emphasizes that the genes modulating the trabecular response to unloading are distinct from those regulating tissue recovery during reloading. The identified QTLs contain the regulatory genes underlying the strong genetic regulation of trabecular bone's sensitivity to weight bearing and may help to identify individuals that are most susceptible to unloading-induced bone loss and/or the least capable of recovering.
