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: 2Citation - Scopus: 2Osteoblasts-Derived Exosomes as Potential Novel Communicators in Particle-Induced Periprosthetic Osteolysis(Elsevier, 2024) de Souza, Wanderson; Gemini-Piperni, S.; Ruivo, Carolina; Bastos, Nuno; Almeida, Sofia; Lopes, Daniel; Ribeiro, Ana R.The inflammatory response to wear particles derived from hip prothesis is considered a hallmark of periprosthetic osteolysis, which can ultimately lead to the need for revision surgery. Exosomes (Exos) have been associated with various bone pathologies, and there is increasing recognition in the literature that they actively transport molecules throughout the body. The role of wear particles in osteoblast-derived Exos is unknown, and the potential contribution of Exos to osteoimmune communication and periprosthetic osteolysis niche is still in its infancy. Given this, we investigate how titanium dioxide nanoparticles (TiO2 NPs), similar in size and composition to prosthetic wear particles, affect Exos biogenesis. Two osteoblastic cell models commonly used to study the response of osteoblasts to wear particles were selected as a proof of concept. The contribution of Exos to periprosthetic osteolysis was assessed by functional assays in which primary human macrophages were stimulated with bone-derived Exos. We demonstrated that TiO2 NPs enter multivesicular bodies, the nascent of Exos, altering osteoblast-derived Exos secretion and molecular cargo. No significant differences were observed in Exos morphology and size. However, functional assays reveal that Exos cargo enriched in uPA stimulates macrophages to a mixed M1 and M2 phenotype, inducing the release of pro- and anti-inflammatory signals characteristic of periprosthetic osteolysis. In addition, we demonstrated the expression of uPA in exosomes derived from the urine of patients with osteolysis. These results suggest that uPA can be a potential biomarker of osteolysis. In the future, uPa may serve as a possible non-invasive biomarker to identify patients at risk for peri-implant osteolysis.Article Citation - WoS: 20Citation - Scopus: 20Preliminary Tribo-Electrochemical and Biological Responses of the Ti-Tib In-Situ Composites Intended for Load-Bearing Biomedical Implants(Elsevier, 2022) Sousa, Lia; Toptan, Fatih; Alves, Alexandra C.; Costa, N. A.; Gemini Piperni, Sara; Rossi, Andre Linhares; Ribeiro, Ana R.; Simöes, Sönia; Toptan, FatihPoor tribocorrosion resistance of Ti and its alloys remains as a concern for load-bearing biomedical implants. Despite being an effective method to improve tribocorrosion resistance, titanium matrix composites (TMCs) have yet to be used in this type of applications. In-situ TiB (titanium boride) and TiC (titanium carbide) reinforcement phases have been considered as one of the best options to produce TMCs once these phases present high compatibility and strong interfacial bonding with Ti. Although the effect of these phases on the mechanical properties of Ti has been thoroughly researched in the last years, their effect on corrosion, tribocorrosion and biocompatibility of Ti is yet to be fully understood. In this work, in-situ Ti-TiB-TiCx composites obtained by reactive hot pressing showed identical corrosion response compared to the unreinforced Ti but displayed improved tribocorrosion behaviour. Under 0.5 N load, composites presented as average a reduction of 51% in wear volume loss and under 10 N the reduction was up to 93%. Early biological tests showed promising results, as composites were biocompatible and induced osteoblasts spreading and possibly proliferation most probably due to composite chemistry and surface hardness.Article Citation - WoS: 8Citation - Scopus: 11Application of Low Intensity Mechanical Vibrations for Bone Tissue Maintenance and Regeneration(TÜBİTAK, 2016) Ölçüm, Melis; Baskan, Öznur; Karadaş, Özge; Özçivici, EnginPhysical 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.Conference Object Citation - WoS: 4Citation - Scopus: 5Application of Magnetic Levitation Induced Weightlessness To Detect Cell Lineage(IEEE, 2019) Sarıgil, Öykü; Anıl İnevi, Müge; Yılmaz, Esra; Çağan, Melike; Meşe, Gülistan; Tekin, Hüseyin Cumhur; Özçivici, EnginIdentification and classification of bone marrow cells is an important step for molecular biology and therapeutic studies related to bone marrow disorders such as osteoporosis or obesity. In this study, we applied magnetic levitation technology to induce a weightlessness environment to detect adipocytes and osteoblasts based on their single cell density. This biotechnological method can be used for separation of heterogeneous populations such as bone marrow once adapted to a continuous microfluidic platform.