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Pyrroloquinoline quinine inhibits RANKL-mediated expression of NFATc1 in part via suppression of c-Fos in mouse bone marrow cells and inhibits wear particle-induced osteolysis in mice.

Abstract
The effects of pyrroloquinoline quinine (PQQ) on RANKL-induced osteoclast differentiation and on wear particle-induced osteolysis were examined in this study. PQQ inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages (BMMs) in a dose-dependent manner without any evidence of cytotoxicity. The mRNA expression of c-Fos, NFATc1, and TRAP in RANKL-treated BMMs was inhibited by PQQ treatment. Moreover, RANKL-induced c-Fos and NFATc1 protein expression was suppressed by PQQ. PQQ additionally inhibited the bone resorptive activity of differentiated osteoclasts. Further a UHMWPE-induced murine calvaria erosion model study was performed to assess the effects of PQQ on wear particle-induced osteolysis in vivo. Mice treated with PQQ demonstrated marked attenuation of bone erosion based on Micro-CT and histologic analysis of calvaria. These results collectively suggested that PQQ demonstrated inhibitory effects on osteoclast differentiation in vitro and may suppress wear particle-induced osteolysis in vivo, indicating that PQQ may therefore serve as a useful drug in the prevention of bone loss.
AuthorsLingbo Kong, Chongfei Yang, Lifeng Yu, Wanli Smith, Shu Zhu, Jinyu Zhu, Qingsheng Zhu
JournalPloS one (PLoS One) Vol. 8 Issue 4 Pg. e61013 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23613773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Isoenzymes
  • NFATC Transcription Factors
  • Polyethylenes
  • Proto-Oncogene Proteins c-fos
  • Pyrroles
  • Quinolines
  • RANK Ligand
  • RNA, Messenger
  • pyrroloquinoline
  • ultra-high molecular weight polyethylene
  • Quinine
  • Acid Phosphatase
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase
Topics
  • Acid Phosphatase (genetics, metabolism)
  • Animals
  • Bone Marrow Cells (drug effects, metabolism)
  • Cell Death (drug effects)
  • Cell Differentiation (drug effects)
  • Gene Expression Regulation (drug effects)
  • Isoenzymes (genetics, metabolism)
  • Mice
  • Mice, Inbred C57BL
  • NFATC Transcription Factors (genetics, metabolism)
  • Osteoclasts (drug effects, metabolism, pathology)
  • Osteogenesis (drug effects)
  • Osteolysis (chemically induced, metabolism, pathology)
  • Polyethylenes (adverse effects)
  • Proto-Oncogene Proteins c-fos (genetics, metabolism)
  • Pyrroles (pharmacology)
  • Quinine (pharmacology)
  • Quinolines (pharmacology)
  • RANK Ligand (pharmacology)
  • RNA, Messenger (genetics, metabolism)
  • Skull (diagnostic imaging, pathology)
  • Tartrate-Resistant Acid Phosphatase
  • X-Ray Microtomography

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