20.500.12556/DiRROS-22624 Insights into the osteosarcoma microenvironment multiscale analysis of structural and mineral heterogeneity Osteosarcoma (OS) is a malignant and heterogeneous disease that typically originates in the long bones of children and adolescents. It is characterized by the presence of immature cells having an aggressive phenotype and rapid uncontrolled proliferation. OS progression induces significant molecular and cellular changes locally within the bone, resulting in the development of an abnormal tumor microenvironment (TME). The OS TME plays a crucial role in tumor progression and development, however, the precise effects of OS on bone structure and mineralization still remain poorly understood. In this study, we examined the OS TME by analyzing samples from osteoblastic, parosteal, and periosteal osteosarcomas. Employing advanced synchrotron-based X-ray techniques, we performed a multiscale analysis to evaluate the structural and mineral complexity of tumor-affected bone. Our results revealed marked morphological differences among the osteosarcoma subtypes, while con- firming that biomineralization remains active through the production of hydroxyapatite (HA). X-ray diffraction identified two distinct hydroxyapatite crystalline phases across all samples, suggesting a critical behavior of minerals in bone. Additionally, we observed that the bone mineral structure in periosteal and parosteal osteosarcomas exhibited crystal deformations along the c-axis, whereas the osteoblastic osteosarcoma displayed a mineral profile comparable to control bone. Micro-X-ray absorption near-edge spectroscopy revealed the occurrence of a dysregulated biomineralization in the parosteal and periosteal subtypes, marked by the presence of calcium compounds different from HA, in contrast to the mature mineral state found in the osteoblastic variant. These findings highlight the complexity of osteosarcoma repercussion on bone tissue, offering new in- sights into the interactions within the OS TME. osteosarcoma biomineralization XANES synchrotron-based X-ray diffraction X-ray computed microtomography osteosarkom biomineralizacija XANES rentgenska difrakcija na osnovi sinhrotrona rentgenska računalniška mikrotomografija true false true Elsevier Ltd. Angleški jezik Slovenski jezik © 2025 The Authors Neznano 2025-06-10 13:56:09 2025-06-10 14:08:55 2025-10-24 03:51:50 0000-00-00 00:00:00 2025 0 0 str. 193-201 Vol. 199 Jun. 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2025-05-01 61 1878-7568 10.1016/j.actbio.2025.04.057 238784259 https://www.sciencedirect.com/science/article/pii/S1742706125003101 1 ea2e3b44-45f1-11f0-963a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=32785 1-s2.0-S1742706125003101-main.pdf 1-s2.0-S1742706125003101-main.pdf 1 BB1C80C40B389E7992EE79E875768452 387e7c6abf6ab86d93f4f9171a8fb56c010e111c7b17d021a122247d44fd6019 9406c1e9-45f3-11f0-963a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=32788 1-s2.0-S1742706125003101-mmc1.docx 1-s2.0-S1742706125003101-mmc1.docx 1 87D4573694F88A9F1CFD78D5A0CAE05F 25b085a6205d8bd5ec48c2b5f4a40326148d067be63c98f62c0dd076f82c4896 a95f43ac-45f3-11f0-963a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=32789 Zavod za gradbeništvo Slovenije 0 0 0