骨愈合
医学
缺氧(环境)
巨噬细胞移动抑制因子
药理学
免疫学
癌症研究
外科
细胞因子
化学
有机化学
氧气
作者
Annemarie Lang,Jonathan Stefanowski,Moritz Pfeiffenberger,Angelique Wolter,Alexandra Damerau,Shabnam Hemmati‐Sadeghi,Rainer Haag,Anja E. Hauser,Max Löhning,Georg N. Duda,Paula Hoff,Katharina Schmidt‐Bleek,Timo Gaber,Frank Buttgereit
出处
期刊:Bone
[Elsevier]
日期:2022-01-01
卷期号:154: 116247-116247
被引量:8
标识
DOI:10.1016/j.bone.2021.116247
摘要
The initial phase of fracture healing is crucial for the success of bone regeneration and is characterized by an inflammatory milieu and low oxygen tension (hypoxia). Negative interference with or prolongation of this fine-tuned initiation phase will ultimately lead to a delayed or incomplete healing such as non-unions which then requires an effective and gentle therapeutic intervention. Common reasons include a dysregulated immune response, immunosuppression or a failure in cellular adaptation to the inflammatory hypoxic milieu of the fracture gap and a reduction in vascularizing capacity by environmental noxious agents (e.g. rheumatoid arthritis or smoking). The hypoxia-inducible factor (HIF)-1α is responsible for the cellular adaptation to hypoxia, activating angiogenesis and supporting cell attraction and migration to the fracture gap. Here, we hypothesized that stabilizing HIF-1α could be a cost-effective and low-risk prevention strategy for fracture healing disorders. Therefore, we combined a well-known HIF-stabilizer - deferoxamine (DFO) - and a less known HIF-enhancer - macrophage migration inhibitory factor (MIF) - to synergistically induce improved fracture healing. Stabilization of HIF-1α enhanced calcification and osteogenic differentiation of MSCs in vitro. In vivo, only the application of DFO without MIF during the initial healing phase increased callus mineralization and vessel formation in a preclinical mouse-osteotomy-model modified to display a compromised healing. Although we did not find a synergistically effect of MIF when added to DFO, our findings provide additional support for a preventive strategy towards bone healing disorders in patients with a higher risk by accelerating fracture healing using DFO to stabilize HIF-1α.
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