Catechin hydrate prevents cadmium-induced collagen downregulation in mesenchymal stem cells via SMAD/RUNX2

儿茶素水合物通过SMAD/RUNX2途径阻止镉诱导的间充质干细胞胶原蛋白下调

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Abstract

BACKGROUND AND PURPOSE: Cadmium (Cd) inhibited osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), while catechin hydrate (CH) improved the osteo-differentiation. Meanwhile, this investigation aimed to study the compensating effect of CH on Cd inhibition. EXPERIMENTAL APPROACH: BMSCs from Wistar rats were treated with Cd and CH, and then the viability and population doubling number were investigated. Based on them, 1.5 μM and 0.25 μM of Cd and CH were chosen, respectively. Following osteogenic induction, matrix production, expression of osteogenic-related genes, and expression of collagen-1 (COL1-A1) protein were analyzed. Moreover, the ability of CH to prevent Cd-induced oxidative stress, as well as the metabolic activity of the treated cells, was evaluated. FINDINGS/RESULTS: The selected concentration of CH significantly ameliorated Cd-induced inhibition of BMSCs osteo-differentiation through preventing oxidative stress and ameliorating gene expression. Indeed, CH in the co-treatment group significantly improved the expression of Smadl, Bmp2, Runx2, Oc, Alp, Col-1 genes as well as the production of COL 1-A1 protein compared to the control group. Moreover, the co-treatment of CH and Cd significantly decreased MDA levels and boosted TAC levels and CAT, SOD activity compared to the control group. CH compensated for the Cd-induced metabolic changes as LDH, ALT, and AST activities significantly improved to the control level. CONCLUSION AND IMPLICATIONS: CH prevented oxidative stress and counteracted the inhibitory effect of Cd on the osteogenic differentiation of BMSCs. Therefore, CH may be suggested to prevent Cd toxicity on bone.

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