骨愈合
医学
材料科学
养生
骨吸收
骨质疏松症
骨矿物
外科
内科学
作者
Lena Batoon,Susan Millard,Liza J. Raggatt,Cheyenne Sandrock,Edmund Pickering,Kyle Williams,Lucas W.H. Sun,Alex Wu,Katharine M. Irvine,Peter Pivonka,Vaida Glatt,Martin Wullschleger,David Hume,Allison R. Pettit
出处
期刊:Biomaterials
[Elsevier]
日期:2021-08-01
卷期号:275: 120936-120936
被引量:11
标识
DOI:10.1016/j.biomaterials.2021.120936
摘要
Macrophage-targeted therapies, including macrophage colony-stimulating factor 1 (CSF1), have been shown to have pro-repair impacts post-fracture. Preclinical/clinical applications of CSF1 have been expedited by development of chimeric CSF1-Fc which has extended circulating half-life. Here, we used mouse models to investigate the bone regenerative potential of CSF1-Fc in healthy and osteoporotic fracture. We also explored whether combination of CSF1-Fc with interleukin (IL)-4 provided additional fracture healing benefit in osteopenic bone. Micro-computed tomography, in situ histomorphometry, and bone mechanical parameters were used to assess systemic impacts of CSF1-Fc therapy in naive mice (male and female young, adult and geriatric). An intermittent CSF1-Fc regimen was optimized to mitigate undesirable impacts on bone resorption and hepatosplenomegaly, irrespective of age or gender. The intermittent CSF1-Fc regimen was tested in a mid-diaphyseal femoral fracture model in healthy bones with treatment initiated 1-day post-fracture. Weekly CSF1-Fc did not impact osteoclasts but increased osteal macrophages and improved fracture strength. Importantly, this treatment regimen also improved fracture union and strength in an ovariectomy-model of delayed fracture repair. Combining CSF1-Fc with IL-4 initiated 1-week post-fracture reduced the efficacy of CSF1-Fc. This study describes a novel strategy to specifically achieve bone regenerative actions of CSF1-Fc that has the potential to alleviate fragility fracture morbidity and mortality.
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