title: Titanium IV ions induced human osteoclast differentiation and enhanced bone resorption in vitro.
abstract: There is increasing evidence that titanium (Ti) ions are released from orthopedic implants, with concentrations in the range of 1 microM in tissue and blood, and may play a role in aseptic loosening of orthopedic implants. This study investigated whether Ti(IV) ions induce differentiation of monocytic osteoclast precursors into osteo-resorptive multinucleated cells and influence the activation and function of in vitro generated osteoclasts. Human monocytes and in vitro generated osteoclasts were exposed to 1 microM Ti(IV) ions for 10 days. Thereafter, osteoclast differentiation, activation, and function were evaluated. Transcription of specific osteoclastic genes was measured using quantitative reverse transcription polymerase chain reactions, which showed increased expression of tartrate-resistant acid phosphatase (TRAP) in approximately 20% of Ti(IV)-treated monocytes. Detection and quantification of intracellular TRAP activity using ELF97 as a fluorescent substrate revealed a significant increase of TRAP-positive cells in Ti(IV)-treated monocytes. Additionally, as demonstrated on dentin slide cultures, Ti(IV)-treated monocytes became functional bone resorbing cells, significantly increasing their osteo-resorptive activity to similar levels as osteoclasts in vitro. These results suggest that Ti(IV) ions released by biocorrosion from orthopedic implants induce differentiation of monocytes toward mature, functional osteoclasts, which may well contribute the pathomechanism of aseptic loosening.
authors.affiliation: School of Anatomy and Human Biology, University of Western Australia, Crawley, Australia. dcadosch@anhb.uwa.edu.au
authors.forename: Dieter
authors.initials: D
authors.lastname: Cadosch
authors.forename: Erwin
authors.initials: E
authors.lastname: Chan
authors.forename: Oliver P
authors.initials: OP
authors.lastname: Gautschi
authors.forename: James
authors.initials: J
authors.lastname: Meagher
authors.forename: René
authors.initials: R
authors.lastname: Zellweger
authors.forename: Luis
authors.initials: L
authors.lastname: Filgueira
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D001862:Bone Resorption; D002454:Cell Differentiation; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D014025:Titanium / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D014025:Titanium; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase