title: 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.
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Lingbo
authors.initials: L
authors.lastname: Kong
authors.forename: Chongfei
authors.initials: C
authors.lastname: Yang
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yu
authors.forename: Wanli
authors.initials: W
authors.lastname: Smith
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.forename: Jinyu
authors.initials: J
authors.lastname: Zhu
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D010014:Osteolysis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011095:Polyethylenes / Q000009:adverse effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D053245:RANK Ligand / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology; D000071681:Tartrate-Resistant Acid Phosphatase; D055114:X-Ray Microtomography
chemical_list: D007527:Isoenzymes; D050778:NFATC Transcription Factors; D011095:Polyethylenes; D016760:Proto-Oncogene Proteins c-fos; D011758:Pyrroles; D011804:Quinolines; D053245:RANK Ligand; D012333:RNA, Messenger; C410406:pyrroloquinoline; C111601:ultra-high molecular weight polyethylene; D011803:Quinine; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase