TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Wei Qiao
  • Karen H. M. Wong
  • Jie Shen
  • Wenhao Wang
  • Jun Wu
  • Jinhua Li
  • Zhengjie Lin
  • Zetao Chen
  • Jukka P. Matinlinna
  • Yufeng Zheng
  • Shuilin Wu
  • Xuanyong Liu
  • Keng Po Lai
  • Zhuofan Chen
  • Kenneth M. C. Cheung
  • Kelvin W. K. Yeung

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Detail(s)

Original languageEnglish
Article number2885
Journal / PublicationNature Communications
Volume12
Issue number1
Online published17 May 2021
Publication statusPublished - 2021

Link(s)

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.

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Citation Format(s)

TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration. / Qiao, Wei; Wong, Karen H. M.; Shen, Jie; Wang, Wenhao; Wu, Jun; Li, Jinhua; Lin, Zhengjie; Chen, Zetao; Matinlinna, Jukka P.; Zheng, Yufeng; Wu, Shuilin; Liu, Xuanyong; Lai, Keng Po; Chen, Zhuofan; Lam, Yun Wah; Cheung, Kenneth M. C.; Yeung, Kelvin W. K.

In: Nature Communications, Vol. 12, No. 1, 2885, 2021.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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