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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...

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Autores principales: Namangkalakul, Worachat, Nagai, Shigenori, Jin, Chengxue, Nakahama, Ken-ichi, Yoshimoto, Yuki, Ueha, Satoshi, Akiyoshi, Kazunari, Matsushima, Kouji, Nakashima, Tomoki, Takechi, Masaki, Iseki, Sachiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387695/
https://www.ncbi.nlm.nih.gov/pubmed/37529250
http://dx.doi.org/10.1177/20417314231187960
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author Namangkalakul, Worachat
Nagai, Shigenori
Jin, Chengxue
Nakahama, Ken-ichi
Yoshimoto, Yuki
Ueha, Satoshi
Akiyoshi, Kazunari
Matsushima, Kouji
Nakashima, Tomoki
Takechi, Masaki
Iseki, Sachiko
author_facet Namangkalakul, Worachat
Nagai, Shigenori
Jin, Chengxue
Nakahama, Ken-ichi
Yoshimoto, Yuki
Ueha, Satoshi
Akiyoshi, Kazunari
Matsushima, Kouji
Nakashima, Tomoki
Takechi, Masaki
Iseki, Sachiko
author_sort Namangkalakul, Worachat
collection PubMed
description 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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spelling pubmed-103876952023-08-01 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 Namangkalakul, Worachat Nagai, Shigenori Jin, Chengxue Nakahama, Ken-ichi Yoshimoto, Yuki Ueha, Satoshi Akiyoshi, Kazunari Matsushima, Kouji Nakashima, Tomoki Takechi, Masaki Iseki, Sachiko J Tissue Eng Original Article 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. SAGE Publications 2023-07-26 /pmc/articles/PMC10387695/ /pubmed/37529250 http://dx.doi.org/10.1177/20417314231187960 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Namangkalakul, Worachat
Nagai, Shigenori
Jin, Chengxue
Nakahama, Ken-ichi
Yoshimoto, Yuki
Ueha, Satoshi
Akiyoshi, Kazunari
Matsushima, Kouji
Nakashima, Tomoki
Takechi, Masaki
Iseki, Sachiko
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387695/
https://www.ncbi.nlm.nih.gov/pubmed/37529250
http://dx.doi.org/10.1177/20417314231187960
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