The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Diabetes Mellitus Induces Bone Marrow Microangiopathy
Open accessAbstract
Objective— The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis. Methods and Results— We found profound structural alterations in BM from mice with type 1 diabetes with depletion of the hematopoietic component and fatty degeneration. Blood flow (fluorescent microspheres) and microvascular density (immunohistochemistry) were remarkably reduced. Flow cytometry verified the depletion of MECA-32 + endothelial cells. Cultured endothelial cells from BM of diabetic mice showed higher levels of oxidative stress, increased activity of the senescence marker β-galactosidase, reduced migratory and network-formation capacities, and increased permeability and adhesiveness to BM mononuclear cells. Flow cytometry analysis of lineage − c-Kit + Sca-1 + cell distribution along an in vivo Hoechst-33342 dye perfusion gradient documented that diabetes depletes lineage − c-Kit + Sca-1 + cells predominantly in the low-perfused part of the marrow. Cell depletion was associated to increased oxidative stress, DNA damage, and activation of apoptosis. Boosting the antioxidative pentose phosphate pathway by benfotiamine supplementation prevented microangiopathy, hypoperfusion, and lineage − c-Kit + Sca-1 + cell depletion. Conclusion— We provide novel evidence for the presence of microangiopathy impinging on the integrity of diabetic BM. These discoveries offer the framework for mechanistic solutions of BM dysfunction in diabetes.
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Cites
FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress
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Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells
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Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells
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Mitochondrial complex III regulates hypoxic activation of HIF
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Cited by
Bone disease in diabetes: another manifestation of microvascular disease?
Shanbhogue, V. V., Hansen, S., Frost, M., Brixen, K., & Hermann, A. P. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30134-1 · Cited by 158
Mohammedi, K., Woodward, M., Marre, M., Colagiuri, S., Cooper, M., Harrap, S., Mancia, G., Poulter, N., Williams, B., Zoungas, S., et al. (2017) · Cardiovascular Diabetology · doi:10.1186/s12933-017-0574-y · Cited by 111
Amadesi, S., Reni, C., Katare, R., Meloni, M., Oikawa, A., Beltrami, A. P., Avolio, E., Cesselli, D., Fortunato, O., Spinetti, G., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.089763 · Cited by 100
Self-citationMyeloid cell dysfunction and the pathogenesis of the diabetic chronic wound
Wicks, K., Torbica, T., & Mace, K. A. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.04.006 · Cited by 93
Andrzejewska, A., Catar, R., Schoon, J., Qazi, T. H., Sass, F. A., Jacobi, D., Blankenstein, A., Reinke, S., Krüger, D., Streitz, M., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02474 · Cited by 89
Metadata
- Authors
- Oikawa, A., Siragusa, M., Quaini, F., Mangialardi, G., Katare, R. G., Caporali, A., van Buul, J. D., van Alphen, F. P. J., Graiani, G., Spinetti, G., Kraenkel, N., Prezioso, L., Emanueli, C., & Madeddu, P.
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2010-03
- Volume
- 30
- Issue
- 3
- Pages
- 498-508
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2150835417
- Cited by
- 231
- References
- 9
- FWCI
- 9.11
- Type
- journal article
- Language
- en
- Open access
- green
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- Oikawa, A., Siragusa, M., Quaini, F., Mangialardi, G., Katare, R. G., Caporali, A., van Buul, J. D., van Alphen, F. P. J., Graiani, G., Spinetti, G., Kraenkel, N., Prezioso, L., Emanueli, C., & Madeddu, P. (2010). Diabetes Mellitus Induces Bone Marrow Microangiopathy. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/atvbaha.109.200154
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