Abstract
Background: Copper-containing biomaterials are increasingly applied for bone regeneration due to their pro-angiogenetic, pro-osteogenetic and antimicrobial properties. Therefore, the effect of Cu2+ on osteoclasts, which play a major role in bone remodeling was studied in detail. Methods: Human primary osteoclasts, differentiated from human monocytes were differentiated or cultivated in the presence of Cu2+. Osteoclast formation and activity were analyzed by measurement of osteoclast-specific enzyme activities, gene expression analysis and resorption assays. Furthermore, the glutathione levels of the cells were checked to evaluate oxidative stress induced by Cu2+. Results: Up to 8 µM Cu2+ did not induce cytotoxic effects. Activity of tartrate-resistant acid phosphatase (TRAP) was significantly increased, while other osteoclast specific enzyme activities were not affected. However, gene expression of TRAP was not upregulated. Resorptive activity of osteoclasts towards dentin was not changed in the presence of 8 µM Cu2+ but decreased in the presence of extracellular bone matrix. When Cu2+ was added to mature osteoclasts TRAP activity was not increased and resorption decreased only moderately. The glutathione level of both differentiating and mature osteoclasts was significantly decreased in the presence of Cu2+. Conclusions: Differentiating and mature osteoclasts react differently to Cu2+. High TRAP activities are not necessarily related to high resorption.
Highlights
The trace element copper (Cu2+) is involved in many physiological processes due to its ability to change oxidation states
The present study analyses the effect of Cu2+ on the activity of osteoclast-specific enzymes, their gene expression and on osteoclastic resorption
Löffler and co-workers investigated the effect of metal ions on monocytes and macrophages
Summary
The trace element copper (Cu2+) is involved in many physiological processes due to its ability to change oxidation states. In a previous study we investigated Cu2+ doped brushite forming calcium phosphate bone cements (together with cements doped with other bioactive metal ions) with respect to their influence on osteoclastic differentiation and resorption [19]. It was shown, that Cu2+ had cytotoxic effects on osteoclasts at a concentration of 17.7 μM. Some of our preliminary investigations concerning this matter revealed a highly significant increase of TRAP activity, when osteoclasts were cultivated in the presence of Cu2+ These unexpected results encouraged us to further study the effect of Cu2+ on osteoclast functionality. High TRAP activities are not necessarily related to high resorption
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