Zinc as a Therapeutic Agent in Bone Regeneration

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Abstract

Zinc is an essential mineral that is required for normal skeletal growth and bone homeostasis. Furthermore, zinc appears to be able to promote bone regeneration. However, the cellular and molecular pathways through which zinc promotes bone growth, homeostasis, and regeneration are poorly understood. Zinc can positively affect chondrocyte and osteoblast functions, while inhibiting osteoclast activity, consistent with a beneficial role for zinc in bone homeostasis and regeneration. Based on the effects of zinc on skeletal cell populations and the role of zinc in skeletal growth, therapeutic approaches using zinc to improve bone regeneration are being developed. This review focuses on the role of zinc in bone growth, homeostasis, and regeneration while providing an overview of the existing studies that use zinc as a bone regeneration therapeutic.

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Zinc requirements and the risks and benefits of zinc supplementation.

Wolfgang Maret, Harold Sandstead (2006)

The adult human contains 2-3g of zinc, about 0.1% of which are replenished daily. On this basis and based on estimates of bioavailability of zinc, dietary recommendations are made for apparently healthy individuals. Absent chemical, functional, and/or physical signs of zinc deficiency are assumed indicative of adequacy. More specific data are seldom available. Changing food preferences and availability, and new food preparation, preservation, and processing technologies may require re-evaluation of past data. Conservative estimates suggest that 25% of the world's population is at risk of zinc deficiency. Most of the affected are poor, and rarely consume foods rich in highly bioavailable zinc, while subsisting on foods that are rich in inhibitors of zinc absorption and/or contain relatively small amounts of bioavailable zinc. In contrast, among the relatively affluent, food choice is a major factor affecting risk of zinc deficiency. An additional problem, especially among the relatively affluent, is risk of chronic zinc toxicity caused by excessive consumption of zinc supplements. High intakes of zinc relative to copper can cause copper deficiency. A major challenge that has not been resolved for maximum health benefit is the proximity of the recommended dietary allowance (RDA) and the reference dose (RfD) for safe intake of zinc. Present recommendations do not consider the numerous dietary factors that influence the bioavailability of zinc and copper, and the likelihood of toxicity from zinc supplements. Thus the current assumed range between safe and unsafe intakes of zinc is relatively narrow. At present, assessment of zinc nutriture is complex, involving a number of chemical and functional measurements that have limitations in sensitivity and specificity. This approach needs to be enhanced so that zinc deficiency or excess can be detected early. An increasing number of associations between diseases and zinc status and apparently normal states of health, where additional zinc might be efficacious to prevent certain conditions, point at the pharmacology of zinc compounds as a promising area. For example, relationships between zinc and diabetes mellitus are an area where research might prove fruitful. In our opinion, a multidisciplinary approach will most likely result in success in this fertile area for translational research.

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Zinc as a Gatekeeper of Immune Function

Inga Wessels, Martina Maywald, Lothar Rink (2017)

After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.

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The essential metals for humans: a brief overview

Maria Zoroddu, Jan Aaseth, Guido Crisponi … (2019)

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Journal ID (nlm-ta): Materials (Basel)

Journal ID (iso-abbrev): Materials (Basel)

Journal ID (publisher-id): materials

Title: Materials

Publisher: MDPI

ISSN (Electronic): 1996-1944

Publication date (Electronic): 12 May 2020

Publication date Collection: May 2020

Volume: 13

Issue: 10

Electronic Location Identifier: 2211

Affiliations

[1 ]Department of Orthopaedics, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA; linss@ 123456njms.rutgers.edu

[2 ]School of Graduate Studies, Rutgers, the State University of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA; dk731@ 123456gsbs.rutgers.edu (D.K.); mht45@ 123456gsbs.rutgers.edu (M.T.)

[3 ]Department of Biological Sciences, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA; jessica.cottrell@ 123456shu.edu

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[* ]Correspondence: oconnojp@ 123456njms.rutgers.edu

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J. Patrick O’Connor https://orcid.org/0000-0002-9708-9405

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Publisher ID: materials-13-02211

DOI: 10.3390/ma13102211

PMC ID: 7287917

PubMed ID: 32408474

SO-VID: bc1a7687-dc5b-48c6-8b26-a744544b1479

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Zinc as a Therapeutic Agent in Bone Regeneration

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cGMP: Generators, Effectors and Therapeutic Implications Conference

Most cited references 201

Zinc requirements and the risks and benefits of zinc supplementation.

Zinc as a Gatekeeper of Immune Function

The essential metals for humans: a brief overview

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