Calcineurin/NFAT signaling pathway mediates titanium particle ‑induced inflammation and osteoclast formation by inhibiting RANKL and M‑CSF in vitro.

Calcineurin/NFAT signaling pathway mediates titanium particle‑induced inflammation and osteoclast formation by inhibiting RANKL and M‑CSF in vitro.
Mol Med Rep. 2017 Sep 29;:
Authors: Zhang Y, Jiang P, Li W, Liu X, Lu Y, Huang Z, Song K
Abstract
Wear particles serve a central role in periprosthetic osteolysis, which leads to the aseptic loosening of prostheses. In the present study a lentiviral vector was constructed to silence macrophage colony stimulating factor (M‑CSF) and receptor activator of nuclear factor κ‑B ligand (RANKL) genes, which synergistically inhibit osteoclast formation and differentiation. To confirm the role of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in osteolysis, we transduced murine macrophage/monocyte RAW264.7 cells with M‑CSF‑short hairpin (sh)RNA‑RANKL‑shRNA. Tumor necrosis factor‑α (TNF‑α) protein levels were evaluated using enzyme‑linked immunosorbent assay. Transduced RAW264.7 cells were cultured in Transwell chambers in the presence of 0.1 mg/ml titanium particles to investigate the capacity of TNF‑α inhibition to reduce wear debris‑induced inflammation. RANKL, M‑CSF, TNF‑α, interleukin (IL)‑1β, IL‑6 and NFATc1 mRNA levels were also assessed by reverse transcription‑quantitative polymerase chain reaction. Osteoclastogenesis was measured by tartrate‑resistant acid phosphatase (TRAP) mRNA quantification. Lentiviral‑mediated double g...

Source: Molecular Medicine Reports - October 11, 2017 Category: Molecular Biology Tags: Mol Med Rep Source Type: research