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Publication : Macrophage Control of Incipient Bone Formation in Diabetic Mice.

First Author  Kang M Year  2020
Journal  Front Cell Dev Biol Volume  8
Pages  596622 PubMed ID  33569378
Mgi Jnum  J:314033 Mgi Id  MGI:6804698
Doi  10.3389/fcell.2020.596622 Citation  Kang M, et al. (2020) Macrophage Control of Incipient Bone Formation in Diabetic Mice. Front Cell Dev Biol 8:596622
abstractText  Both soft and hard tissue wound healing are impaired in diabetes. Diabetes negatively impacts fracture healing, bone regeneration and osseointegration of endosseous implants. The complex physiological changes associated with diabetes often manifest in immunological responses to wounding and repair where macrophages play a prominent role in determining outcomes. We hypothesized that macrophages in diabetes contribute toward impaired osseous wound healing. To test this hypothesis, we compared osseous wound healing in the mouse calvaria defect model using macrophages from C57BL/6J and db/db mice to direct osseous repair in both mouse strains. Initial analyses revealed that db/db mice macrophages showed an inflamed phenotype in its resting state. Incipient bone regeneration evaluated by muCT indicated that bone regeneration was relatively impaired in the db/db mouse calvaria and in the calvaria of C57BL/6J mice supplemented with db/db macrophages. Furthermore, osteogenic differentiation of mouse mesenchymal stem cells was negatively impacted by conditioned medium from db/db mice compared to C57BL/6J mice. Moreover, miR-Seq analysis revealed an altered miRNA composition in db/db macrophages with up regulated pro-inflammatory miRNAs and down regulated anti-inflammatory miRNAs. Overall, this study represents a direct step toward understanding macrophage-mediated regulation of osseous bone regeneration and its impairment in type 2 diabetes mellitus.
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