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Pentamidine Inhibits Titanium Particle-Induced Osteolysis In Vivo and Receptor Activator of Nuclear Factor-κB Ligand-Mediated Osteoclast Differentiation In Vitro
Tissue Engineering and Regenerative Medicine ; (6): 265-273, 2019.
Article in English | WPRIM | ID: wpr-761904
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Osteoclasts / Osteolysis / Pentamidine / Phosphorylation / Skull / Titanium / Acid Phosphatase / Bone and Bones / In Vitro Techniques / Macrophage Colony-Stimulating Factor Type of study: Prognostic study Limits: Animals Language: English Journal: Tissue Engineering and Regenerative Medicine Year: 2019 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Osteoclasts / Osteolysis / Pentamidine / Phosphorylation / Skull / Titanium / Acid Phosphatase / Bone and Bones / In Vitro Techniques / Macrophage Colony-Stimulating Factor Type of study: Prognostic study Limits: Animals Language: English Journal: Tissue Engineering and Regenerative Medicine Year: 2019 Type: Article