成纤维细胞生长因子18通过激活CCL2/CCR2轴对M2巨噬细胞极化增强骨形态发生蛋白2诱导头颅骨愈合的作用。

IF 6.7 1区 工程技术 Q1 CELL & TISSUE ENGINEERING
Worachat Namangkalakul, Shigenori Nagai, Chengxue Jin, Ken-Ichi Nakahama, Yuki Yoshimoto, Satoshi Ueha, Kazunari Akiyoshi, Kouji Matsushima, Tomoki Nakashima, Masaki Takechi, Sachiko Iseki
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引用次数: 0

摘要

成纤维细胞生长因子(Fibroblast growth factor, FGF)信号在多种生物事件中起着重要作用。FGF18是与成骨、软骨形成和骨愈合相关的配体之一。加入FGF18后,骨形态发生蛋白2 (bone morphogenetic protein 2, BMP2)-水凝胶诱导的小鼠临界尺寸颅骨缺损愈合得到稳定。在这里,我们的目的是研究FGF18在颅骨骨愈合模型中的作用。我们首先发现,将FGF18 + BMP2水凝胶应用于颅骨骨缺损可增加抗炎标志物的表达,包括矿化骨形成前与组织愈合相关的M2巨噬细胞(M2- moo)的表达。氯膦酸脂质体对巨噬细胞的消耗阻碍了FGF18的作用。然后,我们通过使用由巨噬细胞前体和骨髓基质细胞组成的小鼠原代骨髓(BM)细胞,研究了FGF18如何诱导m2 - moo极化。体外研究表明,FGF18通过影响骨髓间充质干细胞间接诱导m2 - moj极化。FGF18培养的骨髓间充质干细胞的全转录组分析和中和抗体处理表明,趋化因子趋化因子(c-c motif)配体2 (CCL2)是m2 - moo极化的主要介质。最后,在ccr2缺失小鼠颅骨缺损中,fgf18增强的BMP2促进骨愈合的活性减弱。总之,我们提出了FGF18在头颅骨愈合过程中通过刺激CCL2产生来调节m2 - mo_2的新作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Augmented effect of fibroblast growth factor 18 in bone morphogenetic protein 2-induced calvarial bone healing by activation of CCL2/CCR2 axis on M2 macrophage polarization.

Fibroblast growth factor (FGF) signaling plays essential roles in various biological events. FGF18 is one of the ligands to be associated with osteogenesis, chondrogenesis and bone healing. The mouse critical-sized calvarial defect healing induced by the bone morphogenetic protein 2 (BMP2)-hydrogel is stabilized when FGF18 is added. Here, we aimed to investigate the role of FGF18 in the calvarial bone healing model. We first found that FGF18 + BMP2 hydrogel application to the calvarial bone defect increased the expression of anti-inflammatory markers, including those related to tissue healing M2 macrophage (M2-Mø) prior to mineralized bone formation. The depletion of macrophages with clodronate liposome hindered the FGF18 effect. We then examined how FGF18 induces M2-Mø polarization by using mouse primary bone marrow (BM) cells composed of macrophage precursors and BM stromal cells (BMSCs). In vitro studies demonstrated that FGF18 indirectly induces M2-Mø polarization by affecting BMSCs. Whole transcriptome analysis and neutralizing antibody treatment of BMSC cultured with FGF18 revealed that chemoattractant chemokine (c-c motif) ligand 2 (CCL2) is the major mediator for M2-Mø polarization. Finally, FGF18-augmented activity toward favorable bone healing with BMP2 was diminished in the calvarial defect in Ccr2-deleted mice. Altogether, we suggest a novel role of FGF18 in M2-Mø modulation via stimulation of CCL2 production in calvarial bone healing.

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来源期刊
Journal of Tissue Engineering
Journal of Tissue Engineering Engineering-Biomedical Engineering
CiteScore
11.60
自引率
4.90%
发文量
52
审稿时长
12 weeks
期刊介绍: The Journal of Tissue Engineering (JTE) is a peer-reviewed, open-access journal dedicated to scientific research in the field of tissue engineering and its clinical applications. Our journal encompasses a wide range of interests, from the fundamental aspects of stem cells and progenitor cells, including their expansion to viable numbers, to an in-depth understanding of their differentiation processes. Join us in exploring the latest advancements in tissue engineering and its clinical translation.
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