Macrophage Control of Incipient Bone Formation in Diabetic Mice.
Macrophage Control of Incipient Bone Formation in Diabetic Mice.
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DOI：
10.3389/fcell.2020.596622
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发表时间：
2020
影响因子：
5.5
通讯作者：
Cooper LF
中科院分区：
文献类型：
--
作者：
Kang M;Thalji G;Huang CC;Shirazi S;Lu Y;Ravindran S;Cooper LF
糖尿病患者软组织和硬组织伤口愈合均受损。糖尿病对骨内种植体的骨折愈合、骨再生和骨整合有负面影响。与糖尿病相关的复杂生理变化通常表现为对创伤和修复的免疫反应，其中巨噬细胞在决定结果中发挥重要作用。我们假设糖尿病患者的巨噬细胞导致骨创伤愈合受损。为了检验这一假设，我们比较了小鼠颅骨缺损模型中的骨伤口愈合，使用来自C57 BL/6 J和db/db小鼠的巨噬细胞来指导两种小鼠品系中的骨修复。初步分析显示，db/db小鼠巨噬细胞在其静息状态下显示出发炎表型。通过μCT评价的早期骨再生表明，db/db小鼠颅骨和补充db/db巨噬细胞的C57 BL/6 J小鼠颅骨中的骨再生相对受损。此外，与C57 BL/6 J小鼠相比，db/db小鼠的条件培养基对小鼠间充质干细胞的成骨分化产生负面影响。此外，miR-Seq分析揭示了db/db巨噬细胞中改变的miRNA组成，具有上调的促炎性miRNA和下调的抗炎性miRNA。总的来说，这项研究代表了理解巨噬细胞介导的骨再生调控及其在2型糖尿病中的损害的直接步骤。
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 μCT 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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影响因子：
9.5
作者：
Hu Z;Ma C;Rong X;Zou S;Liu X
通讯作者：
Liu X
影响因子：
5.6
作者：
Cassidy, Fearon C.;Shortiss, Ciara;Coleman, Cynthia M.
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Laschke, Matthias W.
DOI：
10.1152/ajpendo.00378.2011
发表时间：
2011-12-01
影响因子：
5.1
作者：
Hamann, Christine;Goettsch, Claudia;Hofbauer, Lorenz C.
通讯作者：
Hofbauer, Lorenz C.
影响因子：
9.7
作者：
Hu, Zhiai;Ma, Chi;Liu, Xiaohua
通讯作者：
Liu, Xiaohua