Effect of zinc on gene expression in osteoblastic MC3T3-E1 cells: enhancement of Runx2, OPG, and regucalcin mRNA expressions

Abstract

The effect of zinc sulfate on the mRNA expressions in Runx2, osteocalcin, alpha1(I) collagen, insulin-like growth factor-I (IGF-I), transforming growth factor-beta1 (TGF-beta1), osteoprotegerin (OPG), regucalcin, zinc transporter 1 (ZIP1), or glyceroaldehyde-3-phosphate dehydrogenase (G3PDH) in osteoblastic MC3T3-E1 cells in vitro was investigated. Cells with subconfluency were cultured for 48 h in a medium containing either vehicle or zinc sulfate (10(-6)-10(-4) M) without fetal bovine serum. Culture with zinc sulfate (10(-5) M) caused a significant increase in Runx2, OPG, or regucalcin mRNA expressions in the cells, while it did not have a significant effect on osteocalcin, alpha1(I) collagen, IGF-I, TGF-beta1, ZIP1, or G3PDH mRNA expressions. The effect of zinc sulfate (10(-4) M) in increasing Runx2 mRNA expression was seen at 24-72 h after culture. A significant increase in OPG mRNA expression was observed at 24 or 48 h after culture. Regucalcin mRNA expression was significantly increased at 48 or 72 h after culture with zinc sulfate (10(-4) M). The stimulatory effects of zinc sulfate on Runx2, OPG, or regucalcin mRNAs were significantly prevented in the presence of cycloheximide (10(-7) M), an inhibitor of protein synthesis, or 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (10(-6) M), an inhibitor of transcription activity. Culture with beta-alanyl-L-histidinato zinc (10(-5) M) caused a significant increase in Runx2 or regucalcin mRNA expressions, while zinc acexamate (10(-5) M) did not have a significant effect on Runx2, OPG, ZIP1, or regucalcin mRNA expressions. This study demonstrates that zinc sulfate has a role in the enhancement of Runx2, OPG, or regucalcin mRNA expression in osteoblastic cells in vitro, suggesting its role in the regulation of gene expression in the cells.

Zinc balance is critical for NFI‐C mediated regulation of odontoblast differentiation

“…Zinc stimulates bone formation by inducing the expression of osteoblast differentiation marker genes, such as Runx2 and osteoprotegerin, and by inducing ALP activity and Ca deposition [Yamaguchi et al, 2008]. However, in the present study, zinc inhibited or delayed dentin formation.…”

“…Similar to our results, zinc plays a reciprocal role for calcification in bone (hard tissue) and blood vessels (soft tissue). In physiological process of bone formation, zinc enhances skeletal growth; however, in pathological process, zinc deficiency increases the calcification of smooth muscle cells, which is associated with plaque formation [Vattikuti and Towler, 2004;Shen et al, 2008;Yamaguchi et al, 2008].…”

“…Indeed, zinc can promote osteoblastic bone formation and inhibit osteoclastic bone resorption [Yamaguchi et al, 1992[Yamaguchi et al, , 2008. In addition, zinc insufficiency has been related to defective collagen synthesis and delayed skeletal maturation [Prasad and Bose, 1975;Agren, 1991].…”

The Influence of Zinco on Bone Repair: A Literature Review

“…No caso da fosfatase alcalina ocorre uma potencialização da sua ação, 32,35-37 já na enzima aminoaciltRNA sintetase o zinco modifica a expressão dos genes, consequentemente altera a ativação dos fatores de transcrição celular. 39 Com o objetivo de avaliar o efeito do co posto β-alanil-L-histidina de zinco (AHZ) no metabolismo ósseo na diáfise femoral (corpo do osso longo) de ratas ovarectomizadas (procedimento cirúrgico no qual remove-se os ovários das ratas para simular a menopausa). Os autores 40 verificaram que a administração de AHZ pode ter um papel terapêutico no tratamento da osteoporose.…”

“…O efeito do zinco sobre as expressões mRNA no gene de transcrição osteoblástica (Runx2) e em proteínas, Yamaguchi e colaboradores 39 cultivaram células osteoblásticas MC3T3-E em um meio contendo sulfato de zinco por um período de 24-78 horas. Foi observado um aumento na expressão genética em Runx2 e nas proteínas osteoprogeterina e regulcalcin.…”