Calcitonin gene-related peptide enhances distraction osteogenesis by increasing angiogenesis
Publication in refereed journal
香港中文大學研究人員
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摘要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.
出版社接受日期07.05.2020
著者Mi J, Xu J, Yao H, Li X, Tong W, Li Y, Dai B, He X, Chow DHK, Li G, Lui KO, Zhao J, Qin L
期刊名稱Tissue Engineering Part A
出版年份2021
月份1
卷號27
期次1-2
頁次87 - 102
國際標準期刊號1937-3341
電子國際標準期刊號1937-335X
語言英式英語
關鍵詞Calcitonin gene-related peptide, endothelial progenitor cells, angiogenesis
