Journal of Biological Research - Thessaloniki (Apr 2022)
The impact of cadmium exposure on cell parameters, expression of specific genes and mineralization in cultivated human osteoblasts
Abstract
Cadmium (Cd) is a widespread environmental pollutant which negatively affects bone health. The aim of this study was to investigate the impact of Cd exposure on cell parameters, expression of specific genes and mineralization in cultivated human osteoblasts. Osteoblasts were incubated without (control group) or with CdCl2 at final Cd concentrations of 0.1, 2, 5, 10, and 50 μM for 2, 4, 6 or 14 days. Cell viability, morphological changes, alkaline phosphatase activity, mineralization, and an expression of 10 genes associated with osteoblast-specific pathways, oxidative stress and cell death were determined. Osteoblast viability decreased at the highest Cd concentrations (5, 10 and 50 μM) after 4 days of treatment. Our findings specified the threshold of Cd exposure with morphological alterations to 5 μM Cd following 4 days of cultivation. Morphometric measurements revealed significantly decreased size of Cd-treated osteoblasts when compared to the control. The alkaline phosphatase activity was dose-dependent with a reduction at 5 μM Cd after 2 days. Cd concentration of 5 μM significantly down-regulated the expression of COL1A1, ALPL, BGLAP, and GPX1 genes. On the contrary, BAX and SOD1 genes were over-expressed at 0.1, 2, 5 μM Cd and TNFSF11 gene transcripts showed an increase at 0.1-2 μM Cd. No significant impact of Cd exposure on transcription levels of WNT5A, RUNX2, and CASP1 genes was detected. Cd at 0.1 μM stimulated the mineralization, while the dose of 1 μM Cd had no effect. In conclusion, Cd exposure had adverse impact on human osteoblasts viability, morphology and function. On molecular level, it was associated with bone matrix protein synthesis, bone remodelling, cell death, and response to oxidative stress. The lowest dose of Cd had the stimulatory effect on bone mineralization.
Keywords
