ArticleCell communication and signaling : CCS2013
Zinc inhibits osteoclast differentiation by suppression of Ca2+-Calcineurin-NFATc1 signaling pathway.
Article in Cell communication and signaling : CCS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 94 citations in OpenAlex.
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- The Role of Magnesium, Zinc, and Strontium in Osteoporotic Fracture Repair.Bioengineering (Basel, Switzerland) · 2025Review
- Advances in the application and research of biomaterials in promoting bone repair and regeneration through immune modulation.Materials today. Bio · 2025Review
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- Zinc Ameliorates High Pi and Ca-Mediated Osteogenic Differentiation of Mesenchymal Stem Cells.Nutrients · 2024Article
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- Zinc based biodegradable metals for bone repair and regeneration: Bioactivity and molecular mechanisms.Materials today. Bio · 2024Review
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- The Role of Zinc in Bone Tissue Health and Regeneration-a Review.Biological trace element research · 2023Review
- Metallothionein 3 promotes osteoclast differentiation and survival by regulating the intracellular ZnCell death discovery · 2023Article
- Metal Ion-Doped Hydroxyapatite-Based Materials for Bone Defect Restoration.Bioengineering (Basel, Switzerland) · 2023Review
- Carnosine, Zinc and Copper: A Menage a Trois in Bone and Cartilage Protection.International journal of molecular sciences · 2023Review
- The Role of Trace Elements and Minerals in Osteoporosis: A Review of Epidemiological and Laboratory Findings.Biomolecules · 2023Review
- Effect of Nano- and Microzinc Supplementation on the Mineral Composition of Bones of Rats with Induced Mammary Gland Cancer.Foods (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundZinc, an essential trace element, inhibits osteoclast differentiation in vitro and in vivo. The molecular mechanism for the inhibitory effect of zinc, however, is poorly understood. The purpose of this study was to investigate the effect of zinc and determine its molecular mechanism on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in mouse bone marrow-derived monocyte cells (BMMs) and RAW264.7 cells.
resultsIn BMMs, zinc treatment during osteoclast differentiation decreased RANKL-induced osteoclast formation in a dose-dependent manner. We show that zinc suppressed the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 (Nfatc1). Zinc also accumulated phospho-Nfatc1 (p-Nfatc1) in the cytosol in a dose-dependent manner and inhibited the translocation of Nfatc1 to the nucleus in RAW264.7 cells. Zinc suppressed the activities of Nfatc1 in the nucleus without changing the activities of NF-κB in RAW264.7 cells. In contrast, calcineurin activity decreased in response to zinc but its protein level was unchanged. RANKL-induced Ca2+ oscillations were inhibited by zinc treatment, but phospho-phospholipase Cγ1 (p-PLCγ1), the upstream signaling molecule of Ca2+ oscillations, was unaffected. Moreover, a constitutively active form of Nfatc1 obviously rescued suppression of osteoclastogenesis by zinc.
conclusionsTaken together, these results demonstrate for the first time that the inhibitory effect of zinc during osteoclastogesis is caused by suppressing the Ca2+-Calcineurin-NFATc1 signaling pathway. Thus, zinc may be a useful therapeutic candidate for the prevention of bone loss caused by NFATc1 activation in osteoclasts.
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