Zinc deficiency suppresses matrix mineralization and retards osteogenesis transiently with catch-up possibly through Runx 2 modulation

In-Sook Kwun, Young-Eun Cho, Ria-Ann R. Lomeda, Hong-In Shin, Je-Yong Choi, Young-Hee Kang, John Hamilton Beattie

    Research output: Contribution to journalArticle

    96 Citations (Scopus)

    Abstract

    A characteristic sign of zinc deficiency is retarded skeletal growth, but the role of zinc in osteoblasts is not well understood. Two major events for bone formation include osteoblast differentiation by bone market gene expression, which is mainly regulated by bone-specific transcription factor Runx2 and extracellular matrix (ECM) mineralization by Ca deposits for bone nodule formation. We investigated whether zinc deficiency down-regulates bone marker gene transcription and whether this might Occur through modulation of Runx2. We also investigated whether zinc deficiency decreases ECM mineralization in osteoblastic MC3T3-E1 cells. In the presence of 5 mu mol/L TPEN as zinc chelator, zinc deficiency (ZnD: 1 mu mol Zn/L) decreased bone marker gene (collagen type 1, osteopontin, alkaline phosphatase, osteoclacin and parathyroid hormone receptor) expression, as compared to normal osteogenic medium (OSM) or zinc adequate medium (ZnA: 15 mu mol/L) (P<0.05) both at 5 days (proliferation) and 15 days (matrix maturation). Decreased bone marker gene transcription by zinc deficiency could be caused by decreased nuclear Runx2 protein (P = 0.05) and transcript (P<0.05) levels in ZnD. Furthermore, within the first 24 h of differentiation when Runx2 expression is induced, maximal Runx2 mRNA and nuclear protein levels were delayed in ZnD compared to OSM and ZnA. ECM Ca deposition was also lower in ZnD, which was also indirectly confirmed by detection of decreased cellular (synthesized) and medium (secreted) ALP activity as well as matrix ALP activity. Taken together, zinc deficiency attenuated osteogenic activity by decreasing bone marker gene transcription through reduced and delayed Runx2 expression and by decreasing ECM mineralization through inhibition of ALP activity in osteoblasts. Decreased and delayed bone marker gene, Runx2 expression and ECM mineralization in osteoblasts by zinc deficiency can be a potential explanation for the retarded skeletal growth which is the major zinc deficiency syndrome. (C) 2009 Elsevier Inc. All rights reserved.

    Original languageEnglish
    Pages (from-to)732-741
    Number of pages10
    JournalBone
    Volume46
    Issue number3
    Early online date10 Nov 2009
    DOIs
    Publication statusPublished - Mar 2010

    Keywords

    • zinc
    • Runx2
    • osteoblast differentiation gene
    • matrix mineralization
    • osteogenesis
    • in-vitro mineralization
    • L-histidinato zinc
    • growth-factor-I
    • osteoblast differentiation
    • transcription factors
    • gene-expression
    • growing rats
    • MC3T3-E1 cells
    • osteoporosis
    • proteins

    Cite this

    Kwun, I-S., Cho, Y-E., Lomeda, R-A. R., Shin, H-I., Choi, J-Y., Kang, Y-H., & Beattie, J. H. (2010). Zinc deficiency suppresses matrix mineralization and retards osteogenesis transiently with catch-up possibly through Runx 2 modulation. Bone, 46(3), 732-741. https://doi.org/10.1016/j.bone.2009.11.003

    Zinc deficiency suppresses matrix mineralization and retards osteogenesis transiently with catch-up possibly through Runx 2 modulation. / Kwun, In-Sook; Cho, Young-Eun; Lomeda, Ria-Ann R.; Shin, Hong-In; Choi, Je-Yong; Kang, Young-Hee; Beattie, John Hamilton.

    In: Bone, Vol. 46, No. 3, 03.2010, p. 732-741.

    Research output: Contribution to journalArticle

    Kwun, I-S, Cho, Y-E, Lomeda, R-AR, Shin, H-I, Choi, J-Y, Kang, Y-H & Beattie, JH 2010, 'Zinc deficiency suppresses matrix mineralization and retards osteogenesis transiently with catch-up possibly through Runx 2 modulation', Bone, vol. 46, no. 3, pp. 732-741. https://doi.org/10.1016/j.bone.2009.11.003
    Kwun, In-Sook ; Cho, Young-Eun ; Lomeda, Ria-Ann R. ; Shin, Hong-In ; Choi, Je-Yong ; Kang, Young-Hee ; Beattie, John Hamilton. / Zinc deficiency suppresses matrix mineralization and retards osteogenesis transiently with catch-up possibly through Runx 2 modulation. In: Bone. 2010 ; Vol. 46, No. 3. pp. 732-741.
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    abstract = "A characteristic sign of zinc deficiency is retarded skeletal growth, but the role of zinc in osteoblasts is not well understood. Two major events for bone formation include osteoblast differentiation by bone market gene expression, which is mainly regulated by bone-specific transcription factor Runx2 and extracellular matrix (ECM) mineralization by Ca deposits for bone nodule formation. We investigated whether zinc deficiency down-regulates bone marker gene transcription and whether this might Occur through modulation of Runx2. We also investigated whether zinc deficiency decreases ECM mineralization in osteoblastic MC3T3-E1 cells. In the presence of 5 mu mol/L TPEN as zinc chelator, zinc deficiency (ZnD: 1 mu mol Zn/L) decreased bone marker gene (collagen type 1, osteopontin, alkaline phosphatase, osteoclacin and parathyroid hormone receptor) expression, as compared to normal osteogenic medium (OSM) or zinc adequate medium (ZnA: 15 mu mol/L) (P<0.05) both at 5 days (proliferation) and 15 days (matrix maturation). Decreased bone marker gene transcription by zinc deficiency could be caused by decreased nuclear Runx2 protein (P = 0.05) and transcript (P<0.05) levels in ZnD. Furthermore, within the first 24 h of differentiation when Runx2 expression is induced, maximal Runx2 mRNA and nuclear protein levels were delayed in ZnD compared to OSM and ZnA. ECM Ca deposition was also lower in ZnD, which was also indirectly confirmed by detection of decreased cellular (synthesized) and medium (secreted) ALP activity as well as matrix ALP activity. Taken together, zinc deficiency attenuated osteogenic activity by decreasing bone marker gene transcription through reduced and delayed Runx2 expression and by decreasing ECM mineralization through inhibition of ALP activity in osteoblasts. Decreased and delayed bone marker gene, Runx2 expression and ECM mineralization in osteoblasts by zinc deficiency can be a potential explanation for the retarded skeletal growth which is the major zinc deficiency syndrome. (C) 2009 Elsevier Inc. All rights reserved.",
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    AU - Kwun, In-Sook

    AU - Cho, Young-Eun

    AU - Lomeda, Ria-Ann R.

    AU - Shin, Hong-In

    AU - Choi, Je-Yong

    AU - Kang, Young-Hee

    AU - Beattie, John Hamilton

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    N2 - A characteristic sign of zinc deficiency is retarded skeletal growth, but the role of zinc in osteoblasts is not well understood. Two major events for bone formation include osteoblast differentiation by bone market gene expression, which is mainly regulated by bone-specific transcription factor Runx2 and extracellular matrix (ECM) mineralization by Ca deposits for bone nodule formation. We investigated whether zinc deficiency down-regulates bone marker gene transcription and whether this might Occur through modulation of Runx2. We also investigated whether zinc deficiency decreases ECM mineralization in osteoblastic MC3T3-E1 cells. In the presence of 5 mu mol/L TPEN as zinc chelator, zinc deficiency (ZnD: 1 mu mol Zn/L) decreased bone marker gene (collagen type 1, osteopontin, alkaline phosphatase, osteoclacin and parathyroid hormone receptor) expression, as compared to normal osteogenic medium (OSM) or zinc adequate medium (ZnA: 15 mu mol/L) (P<0.05) both at 5 days (proliferation) and 15 days (matrix maturation). Decreased bone marker gene transcription by zinc deficiency could be caused by decreased nuclear Runx2 protein (P = 0.05) and transcript (P<0.05) levels in ZnD. Furthermore, within the first 24 h of differentiation when Runx2 expression is induced, maximal Runx2 mRNA and nuclear protein levels were delayed in ZnD compared to OSM and ZnA. ECM Ca deposition was also lower in ZnD, which was also indirectly confirmed by detection of decreased cellular (synthesized) and medium (secreted) ALP activity as well as matrix ALP activity. Taken together, zinc deficiency attenuated osteogenic activity by decreasing bone marker gene transcription through reduced and delayed Runx2 expression and by decreasing ECM mineralization through inhibition of ALP activity in osteoblasts. Decreased and delayed bone marker gene, Runx2 expression and ECM mineralization in osteoblasts by zinc deficiency can be a potential explanation for the retarded skeletal growth which is the major zinc deficiency syndrome. (C) 2009 Elsevier Inc. All rights reserved.

    AB - A characteristic sign of zinc deficiency is retarded skeletal growth, but the role of zinc in osteoblasts is not well understood. Two major events for bone formation include osteoblast differentiation by bone market gene expression, which is mainly regulated by bone-specific transcription factor Runx2 and extracellular matrix (ECM) mineralization by Ca deposits for bone nodule formation. We investigated whether zinc deficiency down-regulates bone marker gene transcription and whether this might Occur through modulation of Runx2. We also investigated whether zinc deficiency decreases ECM mineralization in osteoblastic MC3T3-E1 cells. In the presence of 5 mu mol/L TPEN as zinc chelator, zinc deficiency (ZnD: 1 mu mol Zn/L) decreased bone marker gene (collagen type 1, osteopontin, alkaline phosphatase, osteoclacin and parathyroid hormone receptor) expression, as compared to normal osteogenic medium (OSM) or zinc adequate medium (ZnA: 15 mu mol/L) (P<0.05) both at 5 days (proliferation) and 15 days (matrix maturation). Decreased bone marker gene transcription by zinc deficiency could be caused by decreased nuclear Runx2 protein (P = 0.05) and transcript (P<0.05) levels in ZnD. Furthermore, within the first 24 h of differentiation when Runx2 expression is induced, maximal Runx2 mRNA and nuclear protein levels were delayed in ZnD compared to OSM and ZnA. ECM Ca deposition was also lower in ZnD, which was also indirectly confirmed by detection of decreased cellular (synthesized) and medium (secreted) ALP activity as well as matrix ALP activity. Taken together, zinc deficiency attenuated osteogenic activity by decreasing bone marker gene transcription through reduced and delayed Runx2 expression and by decreasing ECM mineralization through inhibition of ALP activity in osteoblasts. Decreased and delayed bone marker gene, Runx2 expression and ECM mineralization in osteoblasts by zinc deficiency can be a potential explanation for the retarded skeletal growth which is the major zinc deficiency syndrome. (C) 2009 Elsevier Inc. All rights reserved.

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    KW - Runx2

    KW - osteoblast differentiation gene

    KW - matrix mineralization

    KW - osteogenesis

    KW - in-vitro mineralization

    KW - L-histidinato zinc

    KW - growth-factor-I

    KW - osteoblast differentiation

    KW - transcription factors

    KW - gene-expression

    KW - growing rats

    KW - MC3T3-E1 cells

    KW - osteoporosis

    KW - proteins

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    M3 - Article

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    JF - Bone

    SN - 8756-3282

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