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

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-jB 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 IjBa in BMMs. CONCLUSION: These results indicate that pentamidine is effective in inhibiting osteoclast formation and significantly attenuates wear debris-induced bone loss in mice.

Fermented Oyster Extract Prevents Ovariectomy-Induced Bone Loss and Suppresses Osteoclastogenesis

“…Western blot was performed as reported previously [42]. Briefly, cells were treated with RIPA buffer containing phosphatase and protease inhibitors (Roche Applied Science, Mannheim, Germany).…”

Periprosthetic Osteolysis: Mechanisms, Prevention and Treatment

“…There is strong evidence for the critical role of chronic low-grade inflammation in the mechanism of PPOL [7][8][9]. The evidence comes from in vitro studies [10][11][12][13][14], in vivo experiments [15][16][17][18][19], and analysis of tissues harvested during reoperations [20][21][22][23]. It has been repeatedly demonstrated in vitro and in vivo that after contact between artificially prepared prosthetic byproducts and immune cells, the latter express pro-inflammatory cytokines, chemokines and other substances ( Figure 1).…”

Bobby sox homolog regulates tooth root formation through modulation of dentin sialophosphoprotein

“…The fixed tissues were decalcified in 10% ethylenediaminetetraacetic acid, dehydrated with ethanol, embedded in paraffin, and serially sectioned at a thickness of 6 μm. Staining with hematoxylin–eosin (H&E) was carried out following a routine procedure (Ihn, Kim, Cho, & Park, 2019). For immunostaining, 6‐μm sections were treated with 1% hydrogen peroxide and incubated with a rabbit antibody against Dspp (1:100; Kerafast, Boston, MA) at 4°C overnight.…”

“…Staining with hematoxylin-eosin (H&E) was carried out following a routine procedure (Ihn, Kim, Cho, & Park, 2019). For immunostaining, 6-μm sections were treated with 1% hydrogen peroxide and incubated with a rabbit antibody against Dspp (1:100; Kerafast, Boston, MA) at 4°C overnight.…”