Pentamidine Inhibits Titanium Particle-Induced Osteolysis In Vivo and Receptor Activator of Nuclear Factor-κB Ligand-Mediated Osteoclast Differentiation In Vitro
10.1007/s13770-019-00186-y
- Author:
Hye Jung IHN
1
;
Kiryeong KIM
;
Hye Sung CHO
;
Eui Kyun PARK
Author Information
1. Institute for Hard Tissue and Bio-tooth Regeneration (IHBR), Kyungpook National University, 2177 Dalgubeol-daero, Jung-gu, Daegu 41940, Republic of Korea.
- Publication Type:Original Article
- Keywords:
Pentamidine;
Osteolysis;
Osteoclastogenesis;
Titanium;
RANKL
- MeSH:
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
- From:
Tissue Engineering and Regenerative Medicine
2019;16(3):265-273
- CountryRepublic of Korea
- Language:English
-
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.
