CD47是间充质祖细胞增殖和骨折修复所必需的

IF 14.3 1区 医学 Q1 CELL & TISSUE ENGINEERING
Robert L. Zondervan, Christina A. Capobianco, Daniel C. Jenkins, John D. Reicha, Livia Fredrick, Charles Lam, Jeanna T. Schmanski, Jeffery S. Isenberg, Jaimo Ahn, Ralph S. Marcucio, Kurt D. Hankenson
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引用次数: 0

摘要

CD47是一种普遍存在的多效性细胞表面受体。破坏CD47可增强多种组织的损伤修复,但CD47在骨损伤中的作用尚未被研究。在小鼠闭合性骨折模型中,骨折后10天通过显微计算机断层扫描评估,cd47缺失小鼠的骨痂形成减少,组织学检查显示纤维体积增加。为了了解这种表型的细胞基础,从骨髓中获取间充质祖细胞(MSC)。cd47缺失的MSC显示大成纤维细胞集落形成(CFU-F)减少,增殖明显减少,s期细胞减少,但成骨细胞分化未受影响。然而,与先前的研究一致,cd47缺失的内皮细胞相对于WT细胞表现出更高的增殖。同样,在小鼠缺血性骨折模型中,由于骨折后15天相对于WT的骨减少,cd47缺失小鼠显示骨折愈伤组织大小减小。与我们的体外结果一致,体内EdU标记显示cd47缺失小鼠愈伤组织中细胞增殖减少,而CD31和endomucin染色显示内皮细胞密度增加。最后,给患有缺血性骨折的WT小鼠注射阻断CD47蛋白产生的CD47 morpholino,显示出与CD47缺失小鼠的缺血性骨折相似的愈伤组织表型,这表明这种表型不是由于敲除小鼠的发育变化。因此,在骨愈合过程中抑制CD47可减少非缺血性和缺血性骨折愈合,部分原因是通过减少MSC增殖。此外,CD47破坏引起的内皮细胞增殖和早期血管密度的增加不足以克服MSC功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

CD47 is required for mesenchymal progenitor proliferation and fracture repair

CD47 is required for mesenchymal progenitor proliferation and fracture repair

CD47 is a ubiquitous and pleiotropic cell-surface receptor. Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries. In a murine closed-fracture model, CD47-null mice showed decreased callus bone formation as assessed by microcomputed tomography 10 days post-fracture and increased fibrous volume as determined by histology. To understand the cellular basis for this phenotype, mesenchymal progenitors (MSC) were harvested from bone marrow. CD47-null MSC showed decreased large fibroblast colony formation (CFU-F), significantly less proliferation, and fewer cells in S-phase, although osteoblast differentiation was unaffected. However, consistent with prior research, CD47-null endothelial cells showed increased proliferation relative to WT cells. Similarly, in a murine ischemic fracture model, CD47-null mice showed reduced fracture callus size due to a reduction in bone relative to WT 15 days-post fracture. Consistent with our in vitro results, in vivo EdU labeling showed decreased cell proliferation in the callus of CD47-null mice, while staining for CD31 and endomucin demonstrated increased endothelial cell density. Finally, WT mice with ischemic fracture that were administered a CD47 morpholino, which blocks CD47 protein production, showed a callus phenotype similar to that of ischemic fractures in CD47-null mice, suggesting the phenotype was not due to developmental changes in the knockout mice. Thus, inhibition of CD47 during bone healing reduces both non-ischemic and ischemic fracture healing, in part, by decreasing MSC proliferation. Furthermore, the increase in endothelial cell proliferation and early blood vessel density caused by CD47 disruption is not sufficient to overcome MSC dysfunction.

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来源期刊
Bone Research
Bone Research CELL & TISSUE ENGINEERING-
CiteScore
20.00
自引率
4.70%
发文量
289
审稿时长
20 weeks
期刊介绍: Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.
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