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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acid Phosphatase / genetics
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Acid Phosphatase / metabolism
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Animals
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / metabolism*
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Cell Death / drug effects
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Cell Differentiation / drug effects
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Gene Expression Regulation / drug effects
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Mice
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Mice, Inbred C57BL
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NFATC Transcription Factors / genetics
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NFATC Transcription Factors / metabolism*
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Osteoclasts / drug effects
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Osteoclasts / metabolism
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Osteoclasts / pathology
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Osteogenesis / drug effects
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Osteolysis / chemically induced*
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Osteolysis / metabolism
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Osteolysis / pathology
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Polyethylenes / adverse effects
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / metabolism*
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Pyrroles / pharmacology*
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Quinine / pharmacology*
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Quinolines / pharmacology*
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RANK Ligand / pharmacology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Skull / diagnostic imaging
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Skull / pathology
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Tartrate-Resistant Acid Phosphatase
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X-Ray Microtomography
Substances
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Isoenzymes
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NFATC Transcription Factors
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Polyethylenes
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Proto-Oncogene Proteins c-fos
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Pyrroles
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Quinolines
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RANK Ligand
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RNA, Messenger
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pyrroloquinoline
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ultra-high molecular weight polyethylene
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Quinine
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Acid Phosphatase
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Acp5 protein, mouse
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Tartrate-Resistant Acid Phosphatase
Grants and funding
This work was supported in part by a grant-in-aid for scientific research from the Fourth Military Medical University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.