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.

Biodegradation of a magnesium alloy implant in the intercondylar femoral notch showed an appropriate response to the synovial membrane in a rabbit model in vivo

“…32,33 These may induce hypersensitivity reactions by activation of the immune system, 32,34 and may potentially cause numerous local and systemic negative effects, such as inflammation, infection, pain, effusion, urticaria, or wound healing disorder. 35,36 During the Relative metabolic activity (%) Figure 7.…”

Influence of metal ions on human lymphocytes and the generation of titanium-specific T-lymphocytes

“…Currently, the exact pathophysiologic mechanisms leading to aseptic implant failure (commonly known as aseptic loosening) remain unclear. Aseptic loosening is thought to be caused by increased osteolytic activity at the bone-implant interface, ultimately leading to a loss of fixation (3)(4)(5). Infiltration of adaptive immune cells including B-and T-lymphocytes, dendritic cells and monocytes has been observed in histologic sections of peri-implant tissues retrieved from patients with aseptic loosening (6,7).…”

Bio‐corrosion of stainless steel by osteoclasts—in vitro evidence

“…[12][13][14][15] We have previously demonstrated that metal ions (such as titanium) directly induce the differentiation of osteoclast precursors towards mature OC, able of effective bone resorption. 16 Furthermore, once released into the systemic blood circulation, the metal ions bind to serum proteins and form haptens or hapten-like complexes, which are considered to be relevant antigens recognized by T lymphocytes and candidates for eliciting hypersensitivity reactions. 5,17 Exposed to metal-protein complexes, T lymphocytes proliferate and differentiate to produce effectors such as interleukin (IL)-6, IL-1a/b, interferon-gamma (IFN-g) and tumor necrosis factoralpha (TNF-a) that trigger a particular immune response.…”