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Zinc signal: a new player in osteobiology

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Abstract

Disturbed zinc (Zn) homeostasis in mammals is mainly characterized by impaired bone generation accompanied with growth retardation. However, the underlying mechanisms that determine how Zn controls bone homeostasis remain to be defined. Zn homeostasis is tightly controlled by Zn transporter families. Recent studies have shown that Zn transporter-mediated Zn ion (Zn2+) behaves as a signaling factor, called Zn signal, that exerts a multiple function in cellular events, showing why Zn has a vital effect on mammalian bone growth and regeneration. This perspective put importance on the principal mechanisms of Zn participation in mammalian bone homeostasis, shifting our focus on the role of Zn from simply a nutrient to a signaling molecule that fine-tunes intracellular signaling events.

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Abbreviations

ZIP:

Zrt/Irt-like protein

ZnT:

Zn transporter

Zn2+ :

Zn ion

GPCR:

G protein-coupled receptor

BMP:

Bone morphogenetic protein

TGF-β:

Transforming growth factor-beta

KO:

Knockout

STAT:

Signal transducer and activator for transcription

JAK:

Janus kinase

AE:

Acrodermatitis enteropathica

EDS:

Ehlers–Danlos syndrome

SD-EDS:

Spondylodysplastic EDS

cAMP:

Cyclic adenosine monophosphate

PDE:

Phosphodiesterase

GH:

Growth hormone

IGF-I:

Insulin-like growth factor

GHRH:

Growth hormone-releasing hormone

GHRHR:

Growth hormone-releasing hormone receptor

PTHrP:

Parathyroid hormone-related peptide

PTH1R:

Parathyroid hormone 1 receptor

SMAD:

Contraction of Sma and Mad (mothers against decapentaplegic)

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Acknowledgments

We thank Dr. Toshio Hirano, Mr. Masami Kawamura, Ms. Ayumi Ito, Ms. Mayumi Hara, and Ms. Reiko Kimura for their sincere support and contributions. I also thank Dr. Andrea Superti-Furga for the use of the human case images. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, The Foundation of Growth Science (Fukada), The Kanagawa Nanbyo Study Foundation (Fukada), The Naito Foundation (Fukada), and The Takeda Science Foundation (Furuichi).

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Authors and Affiliations

  1. Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, 230-0045, Japan

    Toshiyuki Fukada & Shintaro Hojyo

  2. Department of Allergy and Immunology, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan

    Toshiyuki Fukada

  3. Laboratory of Laboratory Animal Science and Medicine, Department of Veterinary Medical Science, Faculty of Agriculture, Iwate University, Morioka, 020-8550, Japan

    Tatsuya Furuichi

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  1. Toshiyuki Fukada
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Correspondence to Toshiyuki Fukada.

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Fukada, T., Hojyo, S. & Furuichi, T. Zinc signal: a new player in osteobiology. J Bone Miner Metab 31, 129–135 (2013). https://doi.org/10.1007/s00774-012-0409-6

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