Calcitonin Gene-Related Peptide Enhances Distraction Osteogenesis by Increasing Angiogenesis.

Tissue Engineering Part A Pub Date : 2021-01-01 Epub Date: 2020-11-02 DOI:10.1089/ten.TEA.2020.0009
Jie Mi, Jiankun Xu, Hao Yao, Xisheng Li, Wenxue Tong, Ye Li, Bingyang Dai, Xuan He, Dick Ho Kiu Chow, Gang Li, Kathy O Lui, Jie Zhao, Ling Qin
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引用次数: 39

Abstract

Distraction osteogenesis (DO) is a well-established surgical technique for treating bone defect and limb lengthening. The major drawback of DO is the long treatment period as the external fixator has to be kept in place until consolidation is completed. Calcitonin gene-related peptide (CGRP) has been reported to promote angiogenesis by affecting endothelial progenitor cells (EPCs) in limb ischemia and wound healing. Thus, the goal of this study was to evaluate the angiogenic effect of exogenous CGRP on bone regeneration in a rat DO model. Exogenous CGRP was directly injected into the bone defect after each cycle of distraction in vivo. Microcomputed tomography, biomechanical test, and histological analysis were performed to assess the new bone formation. Angiography and immunofluorescence were performed to assess the formation of blood vessels. CD31+CD144+ EPCs in the bone defect were quantified with flow cytometry. In in vitro study, bone marrow stem cells (BMSCs) were used to investigate the effect of CGRP on EPCs production during endothelial differentiation. Our results showed that CGRP significantly promoted bone regeneration and vessel formation after consolidation. CGRP significantly increased the fraction of CD31+CD144+EPCs and the capillary density in the bone defect at the end of distraction phase. CGRP increased EPC population in the endothelial differentiation of BMSCs in vitro by activating PI3K/AKT signaling pathway. Furthermore, differentiated EPCs rapidly assembled into tube-like structures and promoted osteogenic differentiation of BMSCs. In conclusion, CGRP increased EPC population and promoted blood vessel formation and bone regeneration at the defect region in a DO model. Impact statement Distraction osteogenesis (DO) is a well-established surgical technique for limb lengthening and bone defect. The disadvantage of this technique is that external fixator is needed to be kept in place for about 12 months. This may result in increased risk of infection, financial burden, and negative psychological impacts. In this study, we have injected calcitonin gene-related peptide (CGRP) into the defect region after distraction and found that CGRP enhanced vessel formation and bone regeneration in a rat DO model. This suggests that a controlled delivery system for CGRP could be developed and applied clinically for accelerating bone regeneration in patients with DO.

降钙素基因相关肽通过增加血管生成促进牵张成骨。
牵张成骨术(DO)是一种成熟的治疗骨缺损和肢体延长的外科技术。DO的主要缺点是治疗时间长,因为外固定架必须保持到位,直到完成巩固。据报道,降钙素基因相关肽(CGRP)在肢体缺血和伤口愈合过程中通过影响内皮祖细胞(EPCs)促进血管生成。因此,本研究的目的是评估外源性CGRP对大鼠DO模型骨再生的血管生成作用。体内牵张每个周期后,将外源性CGRP直接注入骨缺损。显微计算机断层扫描,生物力学测试和组织学分析评估新骨形成。血管造影和免疫荧光法评估血管的形成。流式细胞术定量检测骨缺损组织中CD31+CD144+ EPCs。在体外研究中,我们利用骨髓干细胞(BMSCs)来研究CGRP对内皮细胞分化过程中EPCs生成的影响。我们的研究结果显示,CGRP显著促进骨再生和血管形成。CGRP显著增加牵张期末骨缺损中CD31+CD144+EPCs的比例和毛细血管密度。CGRP通过激活PI3K/AKT信号通路,增加体外骨髓间充质干细胞内皮分化中的EPC数量。此外,分化的EPCs迅速组装成管状结构,促进骨髓间充质干细胞的成骨分化。综上所述,CGRP增加了DO模型缺损区EPC数量,促进了缺损区血管形成和骨再生。牵张成骨术(DO)是一种完善的手术技术,用于肢体延长和骨缺损。该技术的缺点是需要将外固定架固定约12个月。这可能导致感染风险增加、经济负担和负面心理影响。在本研究中,我们将降钙素基因相关肽(CGRP)注射到牵张后的缺损区,发现CGRP促进了大鼠DO模型的血管形成和骨再生。这表明CGRP的控制递送系统可以开发并应用于临床,以加速DO患者的骨再生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Tissue Engineering Part A
Tissue Engineering Part A CELL & TISSUE ENGINEERING-BIOTECHNOLOGY & APPLIED MICROBIOLOGY
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