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  An early myeloma bone disease model in skeletally mature mice as a platform for biomaterial characterization of the extracellular matrix

Ziouti, F., Prates Soares, A., Moreno-Jiménez, I., Rack, A., Bogen, B., Cipitria, A., et al. (2020). An early myeloma bone disease model in skeletally mature mice as a platform for biomaterial characterization of the extracellular matrix. Journal of Oncology, 2020: 3985315. doi:10.1155/2020/3985315.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-A9FB-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-C306-7
Genre: Journal Article

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 Creators:
Ziouti, Fani, Author
Prates Soares, Ana, Author
Moreno-Jiménez, Inés1, Author              
Rack, Alexander, Author
Bogen, Bjarne, Author
Cipitria, Amaia1, Author              
Zaslansky, Paul, Author
Jundt, Franziska, Author
Kawano, Yawara, Contributor
Affiliations:
1Amaia Cipitria, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_2489692              

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 Abstract: Multiple myeloma (MM) bone disease is characterized by osteolytic bone tissue destruction resulting in bone pain, fractures, vertebral collapse, and spinal cord compression in patients. Upon initial diagnosis of MM, almost 80% of patients suffer from bone disease. Earlier diagnosis and intervention in MM bone disease would potentially improve treatment outcome and patient survival. New preclinical models are needed for developing novel diagnostic markers of bone structural changes as early as possible in the disease course. Here, we report a proof-of-concept, syngeneic, intrafemoral MOPC315.BM MM murine model in skeletally mature BALB/c mice for detection and characterization of very early changes in the extracellular matrix (ECM) of MM-injected animals. Bioluminescence imaging (BLI) in vivo confirmed myeloma engraftment in 100% of the animals with high osteoclast activity within 21 days after tumor cell inoculation. Early signs of aggressive bone turnover were observed on the outer bone surfaces by high-resolution microcomputed tomography (microCT). Synchrotron phase contrast-enhanced microcomputer tomography (PCE-CT) revealed very local microarchitecture differences highlighting numerous active sites of erosion and new bone at the micrometer scale. Correlative backscattered electron imaging (BSE) and confocal laser scanning microscopy allowed direct comparison of mineralized and nonmineralized matrix changes in the cortical bone. The osteocyte lacunar-canalicular network (OLCN) architecture was disorganized, and irregular-shaped osteocyte lacunae were observed in MM-injected bones after 21 days. Our model provides a potential platform to further evaluate pathological MM bone lesion development at the micro- and ultrastructural levels. These promising results make it possible to combine material science and pharmacological investigations that may improve early detection and treatment of MM bone disease.

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Language(s): eng - English
 Dates: 2020-06-272020
 Publication Status: Published in print
 Pages: -
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 Identifiers: DOI: 10.1155/2020/3985315
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Title: Journal of Oncology
Source Genre: Journal
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Publ. Info: New York : Hindawi
Pages: - Volume / Issue: 2020 Sequence Number: 3985315 Start / End Page: - Identifier: ISBN: 1687-8469