Balogh Enikő, Tóth Andrea, Csiki Dávid Máté, Jeney Viktória
MTA-DE Lendület Vascular Pathophysiology Research Group, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Nutrients. 2024 Nov 23;16(23):4012. doi: 10.3390/nu16234012.
Zinc is the second most abundant trace element in the human body, stored mainly in the bones. Zinc is required for bone growth and homeostasis and is also a crucial cofactor for numerous proteins that play key roles in maintaining microstructural integrity and bone remodeling. Bone marrow-derived mesenchymal stem cells (BMSCs) are multipotent progenitors found in the bone marrow stroma and can differentiate along multiple lineage pathways. In this study, we investigated the effect of zinc on the osteogenic differentiation of BMSCs. We stimulated the osteogenic differentiation of BMSCs with high phosphate and Ca-containing osteogenic medium (PiCa) in the presence or absence of zinc. We followed calcification by measuring ECM mineralization, the Ca content of the ECM, mRNA, and the protein expression of the osteo-chondrogenic transcription factor RUNX2 and SOX9 and its targets OCN and ALP. Zinc dose-dependently abolished PiCa-induced ECM mineralization and decreased the expression of RUNX2, SOX9, OCN, and ALP. Serum albumin did not alter the inhibitory effect of zinc on BMSC mineralization. Our further analysis with the zinc-chelator TPEN and ZnCl confirmed the specific inhibitory effect of free zinc ions on BMSC mineralization. Zinc inhibited phosphate uptake and PiCa-induced upregulation of the sodium-dependent phosphate cotransporters (PiT-1 and PiT-2). Zinc attenuated the PiCa-induced increase in ROS production. Taken together, these data suggest that zinc inhibits PiCa-induced BMSC calcification by regulating phosphate uptake and ROS production.
锌是人体中含量第二丰富的微量元素，主要储存在骨骼中。骨骼生长和内环境稳定需要锌，而且锌也是众多蛋白质的关键辅助因子，这些蛋白质在维持微观结构完整性和骨骼重塑中发挥着关键作用。骨髓间充质干细胞（BMSCs）是存在于骨髓基质中的多能祖细胞，能够沿着多种谱系途径分化。在本研究中，我们调查了锌对BMSCs成骨分化的影响。我们在有或没有锌的情况下，用高磷和含钙的成骨培养基（PiCa）刺激BMSCs的成骨分化。我们通过测量细胞外基质（ECM）矿化、ECM中的钙含量、mRNA以及成骨-软骨生成转录因子RUNX2和SOX9及其靶标骨钙素（OCN）和碱性磷酸酶（ALP）的蛋白质表达来跟踪钙化情况。锌以剂量依赖的方式消除了PiCa诱导的ECM矿化，并降低了RUNX2、SOX9、OCN和ALP的表达。血清白蛋白并未改变锌对BMSC矿化的抑制作用。我们用锌螯合剂三（2-吡啶甲基）胺（TPEN）和氯化锌（ZnCl）进行的进一步分析证实了游离锌离子对BMSC矿化的特异性抑制作用。锌抑制磷酸盐摄取以及PiCa诱导的钠依赖性磷酸盐共转运蛋白（PiT-1和PiT-2）上调。锌减弱了PiCa诱导的活性氧（ROS）生成增加。综上所述，这些数据表明锌通过调节磷酸盐摄取和ROS生成来抑制PiCa诱导的BMSC钙化。
