International orthopaedics · 2014
Inhibitory effects of triptolide on titanium particle-induced osteolysis and receptor activator of nuclear factor-κB ligand-mediated osteoclast differentiation.
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Kim Ju Ang, Ihn Hye Jung, Park Ju-Young, Lim Jiwon, Hong Jung Min, Kim Sang Hyun, Kim Shin-Yoon, Shin Hong-In, Park Eui Kyun
Аннотация
PURPOSE: We examined the effects of triptolide on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and on titanium (Ti) particle-induced osteolysis.
METHODS: To examine the effect of triptolide on osteoclast differentiation, bone marrow macrophages (BMMs) were treated with 100 ng/mL of RANKL and 30 ng/mL of macrophage-colony stimulating factor, or co-cultured with osteoblasts stimulated with 10 nM vitamin D3 and 1 μM prostaglandin E2 in the presence or absence of triptolide (2.8-14 nM). Osteoclast differentiation and activation were assessed using tartrate-resistant acid phosphatase staining, reverse transcriptase-polymerase chain reaction analysis to determine differentiation marker gene expression and pit formation assays. To examine the effect of triptolide on wear debris-induced osteolysis, titanium (Ti) particles were injected into the calvaria of ICR mice. Then, the mice were divided into three groups and were orally administered vehicle, or 16 or 32 μg/kg/day triptolide for ten days, followed by histomorphometric analysis.
RESULTS: Triptolide suppressed RANKL-mediated osteoclast differentiation of BMMs in a dose-dependent manner. In a co-culture system, osteoblasts treated with triptolide could not induce osteoclast differentiation of BMMs, which was accompanied by down-regulation of RANKL and up-regulation of osteoprotegrin. Moreover, triptolide significantly inhibited bone resorption, and expression of the bone resorption marker genes. RANKL-induced activation of p38, ERK, and JNK was substantially inhibited by triptolide. Further, in a Ti-induced mouse calvarial erosion model, mice perorally administrated with triptolide showed significant attenuation of Ti-mediated osteolysis.
CONCLUSION: Our data indicated that triptolide had an anti-osteoclastic effect and significantly suppressed wear debris-induced osteolysis in mice.
METHODS: To examine the effect of triptolide on osteoclast differentiation, bone marrow macrophages (BMMs) were treated with 100 ng/mL of RANKL and 30 ng/mL of macrophage-colony stimulating factor, or co-cultured with osteoblasts stimulated with 10 nM vitamin D3 and 1 μM prostaglandin E2 in the presence or absence of triptolide (2.8-14 nM). Osteoclast differentiation and activation were assessed using tartrate-resistant acid phosphatase staining, reverse transcriptase-polymerase chain reaction analysis to determine differentiation marker gene expression and pit formation assays. To examine the effect of triptolide on wear debris-induced osteolysis, titanium (Ti) particles were injected into the calvaria of ICR mice. Then, the mice were divided into three groups and were orally administered vehicle, or 16 or 32 μg/kg/day triptolide for ten days, followed by histomorphometric analysis.
RESULTS: Triptolide suppressed RANKL-mediated osteoclast differentiation of BMMs in a dose-dependent manner. In a co-culture system, osteoblasts treated with triptolide could not induce osteoclast differentiation of BMMs, which was accompanied by down-regulation of RANKL and up-regulation of osteoprotegrin. Moreover, triptolide significantly inhibited bone resorption, and expression of the bone resorption marker genes. RANKL-induced activation of p38, ERK, and JNK was substantially inhibited by triptolide. Further, in a Ti-induced mouse calvarial erosion model, mice perorally administrated with triptolide showed significant attenuation of Ti-mediated osteolysis.
CONCLUSION: Our data indicated that triptolide had an anti-osteoclastic effect and significantly suppressed wear debris-induced osteolysis in mice.
Предметные рубрики MeSH
Acid PhosphataseAnimalsBlotting, WesternCell DifferentiationCell SurvivalDiterpenesEpoxy CompoundsIsoenzymesMacrophagesMaleMiceMice, Inbred ICROsteoclastsOsteolysisPhenanthrenesReceptor Activator of Nuclear Factor-kappa BReverse Transcriptase Polymerase Chain ReactionSignal TransductionTartrate-Resistant Acid PhosphataseTitanium