Titanium induced production of chemokines CCL17/TARC and CCL22/MDC in human osteoclasts and osteoblasts.
There is increasing evidence that titanium (Ti(IV)) ions are released from orthopedic implants and play a role in aseptic loosening. This study aimed to investigate whether titanium induces expression of chemokines and cytokines that are important in osteoclastogenesis in human osteoclasts and osteoblasts. Incubation of those cells with 1 muM Ti(IV) significantly upregulated expression of CCL17/TARC and CCL22/MDC, RANK-L, M-CSF and pro-inflammatory cytokines as determined by quantitative real-time PCR and ELISA assays. Additionally, flow cytometry was used to show Ti(IV) related increased expression of CCR4, the cognate receptor for CCL17 and CCL22 in challenged osteoclast precursors. These results strongly suggest that Ti(IV) ions play a role in the recruitment of osteoclast precursors to the bone-implant interface by increasing CCL17 and CCL22 expression and by upregulating their cognate receptor. Moreover the increased expression of RANK-L and M-CSF by osteoblasts together with increased levels of pro-inflammatory cytokines may enhance osteoclast differentiation and activity, and subsequently contribute to the pathomechanism of aseptic loosening.
Cadosch
Dieter
D
School of Anatomy and Human Biology, University of Western Australia, Crawley, Western Australia, Australia. dcadosch@gmx.net
Gautschi
Oliver P
OP
Chan
Erwin
E
Simmen
Hans-Peter
HP
Filgueira
Luis
L
D054414:Chemokine CCL17 / Q000096:biosynthesis*; D054422:Chemokine CCL22 / Q000096:biosynthesis*; D003343:Corrosion; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D019736:Prostheses and Implants; D053245:RANK Ligand / Q000096:biosynthesis; D054398:Receptors, CCR4 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014025:Titanium / Q000494:pharmacology*
D054414:Chemokine CCL17; D054422:Chemokine CCL22; D053245:RANK Ligand; D054398:Receptors, CCR4; D016173:Macrophage Colony-Stimulating Factor; D014025:Titanium