Araştırma Çıktıları

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    Loss-of-Function Mutations in ELMO2 Cause Intraosseous Vascular Malformation by Impeding RAC1 Signaling
    (CELL PRESS, 2016-01-01) Cetinkaya, Arda; Xiong, Jingwei Rachel; Vargel, Ibrahim; Kosemehmetoglu, Kemal; Canter, Halil Ibrahim; Gerdan, Omer Faruk; Longo, Nicola; Alzahrani, Ahmad; Camps, Mireia Perez; Taskiran, Ekim Zihni; Laupheimer, Simone; Botto, Lorenzo D.; Paramalingam, Eeswari; Gormez, Zeliha; Uz, Elif; Yuksel, Bayram; Ruacan, Sevket; Sagiroglu, Mahmut Samil; Takahashi, Tokiharu; Reversade, Bruno; Akarsu, Nurten Ayse
    Vascular malformations are non-neoplastic expansions of blood vessels that arise due to errors during angiogenesis. They are a heterogeneous group of sporadic or inherited vascular disorders characterized by localized lesions of arteriovenous, capillary, or lymphatic origin. Vascular malformations that occur inside bone tissue are rare. Herein, we report loss-of-function mutations in ELMO2 (which translates extracellular signals into cellular movements) that are causative for autosomal-recessive intraosseous vascular malformation (VMOS) in five different families. Individuals with VMOS suffer from life-threatening progressive expansion of the jaw, craniofacial, and other intramembranous bones caused by malformed blood vessels that lack a mature vascular smooth muscle layer. Analysis of primary fibroblasts from an affected individual showed that absence of ELMO2 correlated with a significant downregulation of binding partner DOCK1, resulting in deficient RAC1-dependent cell migration. Unexpectedly, elmo2-knockout zebrafish appeared phenotypically normal, suggesting that there might be human-specific ELMO2 requirements in bone vasculature homeostasis or genetic compensation by related genes. Comparative phylogenetic analysis indicated that elmo2 originated upon the appearance of intramembranous bones and the jaw in ancestral vertebrates, implying that elmo2 might have been involved in the evolution of these novel traits. The present findings highlight the necessity of ELMO2 for maintaining vascular integrity, specifically in intramembranous bones.
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    Generation of Bone Tissue Using Adipose Tissue-derived Stem Cells
    (BEZMIALEM VAKIF UNIV, 2021-01-01) Baygol, Emre Gonenc; Guneren, Ethem; Karaaltin, Mehmet Veli; Canter, Halil Ibrahim; Ozturk, Kahraman; Ovali, Ercument; Ozpur, Mustafa Aykut; Yildiz, Kemalettin; Eyuboglu, Fatma
    Objective: Bone grafts and even bone substitutes do not meet all of the requirements of bony reconstructions. The aim of this study was to generate bone tissue from autologous adipose tissue-derived mesenchymal stem cells (ATDMSCs) and decellularised bone allografts. Methods: A 1.5 cm bone defect developed in the middle third of the rabbit's ulna. Reconstructions were carried out using miniplate and screws and interpositional autogenous bone grafts according to the designs of the groups: (1) No touch, (2) cryopreserved, (3) decellularised and (4) ATDMSCs-implanted decellularised bones. Before implantation, ATDMSCs in the last group were labelled with Q-dot and identified microscopically. Results: Graft recovery and irregular callus formation were observed in the first, second and forth groups. In the first group, the organisation of Haversian systems, the structure of the lacunae and the presence of canaliculi ossiums were observed