PMID- 28763481 OWN - NLM STAT- MEDLINE DCOM- 20171010 LR - 20240326 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 8 DP - 2017 TI - Osteoclastic differentiation and resorption is modulated by bioactive metal ions Co2+, Cu2+ and Cr3+ incorporated into calcium phosphate bone cements. PG - e0182109 LID - 10.1371/journal.pone.0182109 [doi] LID - e0182109 AB - Biologically active metal ions in low doses have the potential to accelerate bone defect healing. For successful remodelling the interaction of bone graft materials with both bone-forming osteoblasts and bone resorbing osteoclasts is crucial. In the present study brushite forming calcium phosphate cements (CPC) were doped with Co2+, Cu2+ and Cr3+ and the influence of these materials on osteoclast differentiation and activity was examined. Human osteoclasts were differentiated from human peripheral blood mononuclear cells (PBMC) both on the surface and in indirect contact to the materials on dentin discs. Release of calcium, phosphate and bioactive metal ions was determined using ICP-MS both in the presence and absence of the cells. While Co2+ and Cu2+ showed a burst release, Cr3+ was released steadily at very low concentrations (below 1 muM) and both calcium and phosphate release of the cements was considerably changed in the Cr3+ modified samples. Direct cultivation of PBMC/osteoclasts on Co2+ cements showed lower attached cell number compared to the reference but high activity of osteoclast specific enzymes tartrate resistant acid phosphatase (TRAP), carbonic anhydrase II (CAII) and cathepsin K (CTSK) and significantly increased gene expression of vitronectin receptor. Indirect cultivation with diluted Co2+ cement extracts revealed highest resorbed area compared to all other modifications and the reference. Cu2+ cements had cytotoxic effect on PBMC/osteoclasts during direct cultivation, while indirect cultivation with diluted extracts from Cu2+ cements did not provoke cytotoxic effects but a strictly inhibited resorption. Cr3+ doped cements did not show cytotoxic effects at all. Gene expression and enzyme activity of CTSK was significantly increased in direct culture. Indirect cultivation with Cr3+ doped cements revealed significantly higher resorbed area compared to the reference. In conclusion Cr3+ doped calcium phosphate cements are an innovative cement modification because of their high cytocompatibility and support of active resorption by osteoclasts. FAU - Bernhardt, Anne AU - Bernhardt A AD - Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universitat Dresden, Dresden, Germany. FAU - Schamel, Martha AU - Schamel M AD - Department for Functional Materials in Medicine and Dentistry, University of Wurzburg, Wurzburg, Germany. FAU - Gbureck, Uwe AU - Gbureck U AD - Department for Functional Materials in Medicine and Dentistry, University of Wurzburg, Wurzburg, Germany. FAU - Gelinsky, Michael AU - Gelinsky M AD - Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universitat Dresden, Dresden, Germany. LA - eng PT - Journal Article DEP - 20170801 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Bone Cements) RN - 0 (Calcium Phosphates) RN - 0 (Ions) RN - 0 (Metals) RN - 0R0008Q3JB (Chromium) RN - 3G0H8C9362 (Cobalt) RN - 789U1901C5 (Copper) RN - 97Z1WI3NDX (calcium phosphate) SB - IM MH - Bone Cements/*chemistry MH - Bone Resorption MH - Calcium Phosphates/chemistry MH - Cell Differentiation MH - Cell Survival MH - Chromium/*chemistry MH - Cobalt/*chemistry MH - Copper/*chemistry MH - Humans MH - Inflammation MH - Ions/chemistry MH - Leukocytes, Mononuclear/cytology MH - Metals/chemistry MH - Osteoblasts/metabolism MH - Osteoclasts/*cytology MH - Osteogenesis MH - Stem Cells/cytology PMC - PMC5538673 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/08/02 06:00 MHDA- 2017/10/11 06:00 PMCR- 2017/08/01 CRDT- 2017/08/02 06:00 PHST- 2017/03/26 00:00 [received] PHST- 2017/07/12 00:00 [accepted] PHST- 2017/08/02 06:00 [entrez] PHST- 2017/08/02 06:00 [pubmed] PHST- 2017/10/11 06:00 [medline] PHST- 2017/08/01 00:00 [pmc-release] AID - PONE-D-17-11805 [pii] AID - 10.1371/journal.pone.0182109 [doi] PST - epublish SO - PLoS One. 2017 Aug 1;12(8):e0182109. doi: 10.1371/journal.pone.0182109. eCollection 2017.