CGRP promotes osteogenic differentiation by regulating macrophage M2 polarization through HDAC6/AKAP12 signaling pathway.

IF 2.4 4区 医学 Q4 CELL & TISSUE ENGINEERING Regenerative medicine Pub Date : 2024-01-01 Epub Date: 2024-07-29 DOI:10.1080/17460751.2024.2370697
Wenjing Chen, Lin Ma, Wencai Sun, Wenlong Xiao, Hao Guo, Jiang Xiu, Xin Jiang
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Abstract

Aim: To determine the mechanism of Calcitonin gene-related peptide (CGRP) in bone healing.Materials & methods: Alkaline phosphatase (ALP) activity and inflammatory-factor levels were detected using ELISA. Osteogenic differentiation was assessed using Alizarin red staining technique. The interaction between histone deacetylase 6 (HDAC6) and A-kinase anchoring protein 12 (AKAP12) was investigated through Co- immunoprecipitation.Results: CGRP treatment promoted rat bone marrow-derived macrophages (BMDMs) M2 polarization. CGRP facilitated osteogenic differentiation by enhancing M2 polarization of BMDMs. Mechanistically, CGRP promoted AKAP12 acetylation to activate the extracellular regulated protein kinases pathway by HDAC6 inhibition.Conclusion: CGRP promoted M2 polarization of rat BMDMs and facilitated osteogenic differentiation through the HDAC6/AKAP12/extracellular regulated protein kinases signaling pathway, thereby promoting bone healing.

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CGRP 通过 HDAC6/AKAP12 信号通路调节巨噬细胞 M2 极化,从而促进成骨分化。
目的:确定降钙素基因相关肽(CGRP)在骨愈合中的作用机制。材料与方法:用酶联免疫吸附法检测碱性磷酸酶(ALP)活性和炎症因子水平。使用茜素红染色技术评估成骨分化。通过共免疫沉淀法研究组蛋白去乙酰化酶6(HDAC6)和A-激酶锚定蛋白12(AKAP12)之间的相互作用。结果CGRP 可促进大鼠骨髓源性巨噬细胞(BMDMs)的 M2 极化。CGRP 通过增强 BMDMs 的 M2 极化促进成骨分化。从机制上讲,CGRP通过抑制HDAC6促进AKAP12乙酰化以激活细胞外调节蛋白激酶通路。结论CGRP能促进大鼠BMDMs的M2极化,并通过HDAC6/AKAP12/细胞外调节蛋白激酶信号通路促进成骨分化,从而促进骨愈合。
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来源期刊
Regenerative medicine
Regenerative medicine 医学-工程:生物医学
CiteScore
4.20
自引率
3.70%
发文量
82
审稿时长
6-12 weeks
期刊介绍: Regenerative medicine replaces or regenerates human cells, tissue or organs, to restore or establish normal function*. Since 2006, Regenerative Medicine has been at the forefront of publishing the very best papers and reviews covering the entire regenerative medicine sector. The journal focusses on the entire spectrum of approaches to regenerative medicine, including small molecule drugs, biologics, biomaterials and tissue engineering, and cell and gene therapies – it’s all about regeneration and not a specific platform technology. The journal’s scope encompasses all aspects of the sector ranging from discovery research, through to clinical development, through to commercialization. Regenerative Medicine uniquely supports this important area of biomedical science and healthcare by providing a peer-reviewed journal totally committed to publishing the very best regenerative medicine research, clinical translation and commercialization. Regenerative Medicine provides a specialist forum to address the important challenges and advances in regenerative medicine, delivering this essential information in concise, clear and attractive article formats – vital to a rapidly growing, multidisciplinary and increasingly time-constrained community. Despite substantial developments in our knowledge and understanding of regeneration, the field is still in its infancy. However, progress is accelerating. The next few decades will see the discovery and development of transformative therapies for patients, and in some cases, even cures. Regenerative Medicine will continue to provide a critical overview of these advances as they progress, undergo clinical trials, and eventually become mainstream medicine.
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