title: Inhibitory effects of triptolide on titanium particle-induced osteolysis and receptor activator of nuclear factor-κB ligand-mediated osteoclast differentiation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our data indicated that triptolide had an anti-osteoclastic effect and significantly suppressed wear debris-induced osteolysis in mice.
authors.affiliation: Department of Oral Pathology, IHBR, School of Dentistry, Kyungpook National University, 2177 Dalgubeol daero, Jung gu, Daegu, 700-412, South Korea.
authors.forename: Ju Ang
authors.initials: JA
authors.lastname: Kim
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Ihn
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Jiwon
authors.initials: J
authors.lastname: Lim
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Hong
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Shin-Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Hong-In
authors.initials: HI
authors.lastname: Shin
authors.forename: Eui Kyun
authors.initials: EK
authors.lastname: Park
mesh_terms: D000135:Acid Phosphatase; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D007527:Isoenzymes; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010014:Osteolysis / Q000139:chemically induced*; D010616:Phenanthrenes / Q000494:pharmacology*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D000071681:Tartrate-Resistant Acid Phosphatase; D014025:Titanium / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D007527:Isoenzymes; D010616:Phenanthrenes; D053246:Receptor Activator of Nuclear Factor-kappa B; C001899:triptolide; D014025:Titanium; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase