Tissue Eng Regen Med.  2019 Jun;16(3):265-273. 10.1007/s13770-019-00186-y.

Pentamidine Inhibits Titanium Particle-Induced Osteolysis In Vivo and Receptor Activator of Nuclear Factor-κB Ligand-Mediated Osteoclast Differentiation In Vitro

• Ihn HJ
• Kim K
• Cho HS
• Park EK

• KMID: 2449237
• DOI: http://doi.org/10.1007/s13770-019-00186-y

Abstract

BACKGROUND
Wear debris-induced osteolysis leads to periprosthetic loosening and subsequent prosthetic failure. Since excessive osteoclast formation is closely implicated in periprosthetic osteolysis, identification of agents to suppress osteoclast formation and/or function is crucial for the treatment and prevention of wear particle-induced bone destruction. In this study, we examined the potential effect of pentamidine treatment on titanium (Ti) particle-induced osteolysis, and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis.
METHODS
The effect of pentamidine treatment on bone destruction was examined in Ti particle-induced osteolysis mouse model. Ti particles were implanted onto mouse calvaria, and vehicle or pentamidine was administered for 10 days. Then, calvarial bone tissue was analyzed using micro-computed tomography and histology. We performed in vitro osteoclastogenesis assay using bone marrow-derived macrophages (BMMs) to determine the effect of pentamidine on osteoclast formation. BMMs were treated with 20 ng/mL RANKL and 10 ng/mL macrophage colony-stimulating factor in the presence or absence of pentamidine. Osteoclast differentiation was determined by tartrate-resistant acid phosphatase staining, real-time polymerase chain reaction, and immunofluorescence staining.
RESULTS
Pentamidine administration decreased Ti particle-induced osteoclast formation significantly and prevented bone destruction compared to the Ti particle group in vivo. Pentamidine also suppressed RANKL-induced osteoclast differentiation and actin ring formation markedly, and inhibited the expression of nuclear factor of activated T cell c1 and osteoclast-specific genes in vitro. Additionally, pentamidine also attenuated RANKL-mediated phosphorylation of IκBα in BMMs.
CONCLUSION
These results indicate that pentamidine is effective in inhibiting osteoclast formation and significantly attenuates wear debris-induced bone loss in mice.

Keyword

Pentamidine; Osteolysis; Osteoclastogenesis; Titanium; RANKL

MeSH Terms

Acid Phosphatase
Actins
Animals
Bone and Bones
Fluorescent Antibody Technique
In Vitro Techniques*
Macrophage Colony-Stimulating Factor
Macrophages
Mice
Osteoclasts*
Osteolysis*
Pentamidine*
Phosphorylation
Real-Time Polymerase Chain Reaction
Skull
Titanium*
Acid Phosphatase
Actins
Macrophage Colony-Stimulating Factor
Pentamidine
Titanium