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- Publisher Website: 10.1038/s41467-021-23005-2
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Article: TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration
Title | TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration |
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Authors | |
Issue Date | 2021 |
Publisher | Nature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html |
Citation | Nature Communications, 2021, v. 12, article no. 2885 How to Cite? |
Abstract | Despite the widespread observations on the osteogenic effects of magnesium ion (Mg2+), the diverse roles of Mg2+ during bone healing have not been systematically dissected. Here, we reveal a previously unknown, biphasic mode of action of Mg2+ in bone repair. During the early inflammation phase, Mg2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7), and a TRPM7-dependent influx of Mg2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines, leading to the formation of a pro-osteogenic immune microenvironment. In the later remodeling phase, however, the continued exposure of Mg2+ not only lead to the over-activation of NF-κB signaling in macrophages and increased number of osteoclastic-like cells but also decelerates bone maturation through the suppression of hydroxyapatite precipitation. Thus, the negative effects of Mg2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg2+. Taken together, this study establishes a paradigm shift in the understanding of the diverse and multifaceted roles of Mg2+ in bone healing. |
Persistent Identifier | http://hdl.handle.net/10722/303992 |
ISSN | 2023 Impact Factor: 14.7 2023 SCImago Journal Rankings: 4.887 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Qiao, W | - |
dc.contributor.author | Wong, KHM | - |
dc.contributor.author | Shen, J | - |
dc.contributor.author | Wang, W | - |
dc.contributor.author | Wu, J | - |
dc.contributor.author | Li, J | - |
dc.contributor.author | Lin, Z | - |
dc.contributor.author | Chen, Z | - |
dc.contributor.author | Matinlinna, JP | - |
dc.contributor.author | Zheng, Y | - |
dc.contributor.author | Wu, S | - |
dc.contributor.author | Liu, X | - |
dc.contributor.author | Lai, KP | - |
dc.contributor.author | Chen, Z | - |
dc.contributor.author | Lam, YW | - |
dc.contributor.author | Cheung, KMC | - |
dc.contributor.author | Yeung, KWK | - |
dc.date.accessioned | 2021-09-23T08:53:42Z | - |
dc.date.available | 2021-09-23T08:53:42Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Nature Communications, 2021, v. 12, article no. 2885 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/10722/303992 | - |
dc.description.abstract | Despite the widespread observations on the osteogenic effects of magnesium ion (Mg2+), the diverse roles of Mg2+ during bone healing have not been systematically dissected. Here, we reveal a previously unknown, biphasic mode of action of Mg2+ in bone repair. During the early inflammation phase, Mg2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7), and a TRPM7-dependent influx of Mg2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines, leading to the formation of a pro-osteogenic immune microenvironment. In the later remodeling phase, however, the continued exposure of Mg2+ not only lead to the over-activation of NF-κB signaling in macrophages and increased number of osteoclastic-like cells but also decelerates bone maturation through the suppression of hydroxyapatite precipitation. Thus, the negative effects of Mg2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg2+. Taken together, this study establishes a paradigm shift in the understanding of the diverse and multifaceted roles of Mg2+ in bone healing. | - |
dc.language | eng | - |
dc.publisher | Nature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html | - |
dc.relation.ispartof | Nature Communications | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration | - |
dc.type | Article | - |
dc.identifier.email | Qiao, WW: drqiao@hku.hk | - |
dc.identifier.email | Cheung, KMC: cheungmc@hku.hk | - |
dc.identifier.email | Yeung, KWK: wkkyeung@hku.hk | - |
dc.identifier.authority | Cheung, KMC=rp00387 | - |
dc.identifier.authority | Yeung, KWK=rp00309 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/s41467-021-23005-2 | - |
dc.identifier.pmid | 34001887 | - |
dc.identifier.pmcid | PMC8128914 | - |
dc.identifier.scopus | eid_2-s2.0-85106306570 | - |
dc.identifier.hkuros | 325212 | - |
dc.identifier.volume | 12 | - |
dc.identifier.spage | article no. 2885 | - |
dc.identifier.epage | article no. 2885 | - |
dc.identifier.isi | WOS:000658736300003 | - |
dc.publisher.place | United Kingdom | - |