The inhibition of Wnt signaling attenuates RANKL-induced osteoclastogenic macrophage activation
Abdominal aortic aneurysms (AAAs) have been linked to the activation of osteoclastogenic macrophages. Reports have suggested that Wnt signaling has a dual effect of proliferation and differentiation during osteoclastogenesis. The Wnt/β-Catenin pathway is a critical regulator of cell pluripotency, ce...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2023-07-01
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| Series: | Vascular Biology |
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| Online Access: | https://vb.bioscientifica.com/view/journals/vb/5/1/VB-23-0007.xml |
| _version_ | 1797776083260538880 |
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| author | Dai Yamanouchi Kimihiro Igari |
| author_facet | Dai Yamanouchi Kimihiro Igari |
| author_sort | Dai Yamanouchi |
| collection | DOAJ |
| description | Abdominal aortic aneurysms (AAAs) have been linked to the activation of osteoclastogenic macrophages. Reports have suggested that Wnt signaling has a dual effect of proliferation and differentiation during osteoclastogenesis. The Wnt/β-Catenin pathway is a critical regulator of cell pluripotency, cell survival, and cell fate decisions. It regulates cell proliferation and differentiation through transcriptional co-activators, CBP, and p300, respectively. The inhibition of β-catenin suppresses proliferation but induces differentiation of osteoclast precursor cells. This study aimed to examine the effect of ICG-001, a β-catenin/ CBP-specific Wnt signaling inhibitor, on osteoclastogenesis by inhibiting proliferation without inducing differentiation. To induce osteoclastogenesis, RAW 264.7 macrophages were stimulated with a soluble receptor activator of NF-κB ligand (RANKL). The effect of Wnt signaling inhibition was examined by treating macrophages with or without ICG- 001 during RANKL stimulation. The activation and differentiation of macrophages were examined through western blotting, quantitative PCR, and tartrate-resistant acid phosphate (TRAP) staining in vitro. The relative expression level of the nuclear factor of activated T-cells cytoplasmic 1 protein was significantly suppressed by ICG-001 treatment. The relative expression levels of mRNA of TRAP, cathepsin K, and matrix metalloproteinase-9 were significantly lower in the ICG-001-treated group. The number of TRAP-positive cells decreased in the ICG-001-treated group relative to the non-treated group. The inhibition of Wnt signaling pathway via ICG-001 suppressed osteoclastogenic macrophage activation. Our previous studies have shown the importance of osteoclastogenic macrophage activation in AAA. Further research to examine the therapeutic potential of ICG-001 on AAA is warranted. |
| first_indexed | 2024-03-12T22:44:52Z |
| format | Article |
| id | doaj.art-1813b77e2d6a495d9fde51de0b05959f |
| institution | Directory Open Access Journal |
| issn | 2516-5658 |
| language | English |
| last_indexed | 2024-03-12T22:44:52Z |
| publishDate | 2023-07-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Vascular Biology |
| spelling | doaj.art-1813b77e2d6a495d9fde51de0b05959f2023-07-21T06:25:50ZengBioscientificaVascular Biology2516-56582023-07-015118https://doi.org/10.1530/VB-23-0007The inhibition of Wnt signaling attenuates RANKL-induced osteoclastogenic macrophage activationDai Yamanouchi0Kimihiro Igari1Department of Surgery, Division of Vascular Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Department of Vascular Surgery, Fujita Health University, Toyoake City, Japan Department of Surgery, Division of Vascular Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USAAbdominal aortic aneurysms (AAAs) have been linked to the activation of osteoclastogenic macrophages. Reports have suggested that Wnt signaling has a dual effect of proliferation and differentiation during osteoclastogenesis. The Wnt/β-Catenin pathway is a critical regulator of cell pluripotency, cell survival, and cell fate decisions. It regulates cell proliferation and differentiation through transcriptional co-activators, CBP, and p300, respectively. The inhibition of β-catenin suppresses proliferation but induces differentiation of osteoclast precursor cells. This study aimed to examine the effect of ICG-001, a β-catenin/ CBP-specific Wnt signaling inhibitor, on osteoclastogenesis by inhibiting proliferation without inducing differentiation. To induce osteoclastogenesis, RAW 264.7 macrophages were stimulated with a soluble receptor activator of NF-κB ligand (RANKL). The effect of Wnt signaling inhibition was examined by treating macrophages with or without ICG- 001 during RANKL stimulation. The activation and differentiation of macrophages were examined through western blotting, quantitative PCR, and tartrate-resistant acid phosphate (TRAP) staining in vitro. The relative expression level of the nuclear factor of activated T-cells cytoplasmic 1 protein was significantly suppressed by ICG-001 treatment. The relative expression levels of mRNA of TRAP, cathepsin K, and matrix metalloproteinase-9 were significantly lower in the ICG-001-treated group. The number of TRAP-positive cells decreased in the ICG-001-treated group relative to the non-treated group. The inhibition of Wnt signaling pathway via ICG-001 suppressed osteoclastogenic macrophage activation. Our previous studies have shown the importance of osteoclastogenic macrophage activation in AAA. Further research to examine the therapeutic potential of ICG-001 on AAA is warranted.https://vb.bioscientifica.com/view/journals/vb/5/1/VB-23-0007.xmlmacrophageaneurysmwnt signalingcreb-binding protein (cbp)osteoclastogenesis |
| spellingShingle | Dai Yamanouchi Kimihiro Igari The inhibition of Wnt signaling attenuates RANKL-induced osteoclastogenic macrophage activation Vascular Biology macrophage aneurysm wnt signaling creb-binding protein (cbp) osteoclastogenesis |
| title | The inhibition of Wnt signaling attenuates RANKL-induced osteoclastogenic macrophage activation |
| title_full | The inhibition of Wnt signaling attenuates RANKL-induced osteoclastogenic macrophage activation |
| title_fullStr | The inhibition of Wnt signaling attenuates RANKL-induced osteoclastogenic macrophage activation |
| title_full_unstemmed | The inhibition of Wnt signaling attenuates RANKL-induced osteoclastogenic macrophage activation |
| title_short | The inhibition of Wnt signaling attenuates RANKL-induced osteoclastogenic macrophage activation |
| title_sort | inhibition of wnt signaling attenuates rankl induced osteoclastogenic macrophage activation |
| topic | macrophage aneurysm wnt signaling creb-binding protein (cbp) osteoclastogenesis |
| url | https://vb.bioscientifica.com/view/journals/vb/5/1/VB-23-0007.xml |
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