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: 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: 21Breast Cancer Cells and Macrophages in a Paracrine-Juxtacrine Loop(Elsevier, 2021) Önal, Sevgi; Türker Burhan, Merve; Batı Ayaz, Gizem; Yanık, Hamdullah; Pesen Okvur, DevrimBreast cancer cells (BCC) and macrophages are known to interact via epidermal growth factor (EGF) produced by macrophages and colony stimulating factor-1 (CSF-1) produced by BCC. Despite contradictory findings, this interaction is perceived as a paracrine loop. Further, the underlying mechanism of interaction remains unclear. Here, we investigated interactions of BCC with macrophages in 2D and 3D. While both BCC and macrophages showed invasion/chemotaxis to fetal bovine serum, only macrophages showed chemotaxis to BCC in custom designed 3D cell-on-a-chip devices. These results were in agreement with gradient simulation results and ELISA results showing that macrophage-derived-EGF was not secreted into macrophage-conditioned-medium. Live cell imaging of BCC in the presence and absence of iressa showed that macrophages but not macrophage-derived-matrix modulated adhesion and motility of BCC in 2D. 3D co-culture experiments in collagen and matrigel showed that BCC changed their multicellular organization in the presence of macrophages. In custom designed 3D co-culture cell-on-a-chip devices, macrophages promoted and reduced migration of BCC in collagen and matrigel, respectively. Furthermore, adherent but not suspended BCC endocytosed EGFR when in contact with macrophages. Collectively, our data revealed that macrophages showed chemotaxis towards BCC whereas BCC required direct contact to interact with macrophage-derived-EGF. Therefore, we propose that the interaction between cancer cells and macrophages is a paracrine-juxtacrine loop of CSF-1 and EGF, respectively. © 2020 Elsevier Ltd