title: Anti-osteoclastogenesis of Mineral Trioxide Aggregate through Inhibition of the Autophagic Pathway.
abstract: BACKGROUND
  Mineral trioxide aggregate (MTA) regulates bone remodeling, particularly osteoclast differentiation. However, intracellular mechanisms underlying the anti-osteoclastogenesis of MTA remain unclear. This study aimed to evaluate the potential alterations of autophagic pathway during anti-osteoclastogenic effects by MTA in vitro and investigate their underlying mechanisms.
  
  
  METHODS
  Osteoclast precursors were treated with MTA extracts containing the receptor activator of nuclear factor-kappa B ligand (RANKL). Rapamycin was used to activate autophagy. RANKL-induced osteoclast differentiation was stained with tartrate-resistant acid phosphatase. Several specific autophagy features in osteoclast precursors were measured by using immunofluorescence, monodansylcadaverine, and transmission electron microscope. Autophagy-related proteins were investigated via Western blot analysis. The mRNA expression involved in autophagic and osteoclastic activities was detected with quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  MTA extracts inhibited osteoclast differentiation via preventing the fusion of osteoclast precursors without cytotoxicity. MTA extracts interrupted RANKL-induced acidic vesicular organelle formation and autophagic vacuole appearance in osteoclast precursors. Moreover, autophagic genes and proteins stimulated with RANKL diminished with MTA extracts. Notably, autophagy activation through rapamycin promoted multinucleated osteoclasts formation and increased osteoclastic genes expression, which almost reversed MTA-mediated anti-osteoclastogenic effects.
  
  
  CONCLUSIONS
  MTA inhibited osteoclastogenesis for bone repair through attenuating the autophagic pathway.
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Cheng
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Lingxin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Yu
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Lv
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Guojing
authors.initials: G
authors.lastname: Liu
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: phs301@vip.163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Peng
mesh_terms: D000354:Africa, Western; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D017610:Calcium Compounds / Q000494:pharmacology*; D004338:Drug Combinations; D005455:Fluorescent Antibody Technique; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010010:Osteoclasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology*; D053245:RANK Ligand / Q000494:pharmacology; D000067996:RAW 264.7 Cells / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D017640:Silicates / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D017607:Aluminum Compounds; D017610:Calcium Compounds; D004338:Drug Combinations; D010087:Oxides; D053245:RANK Ligand; D017640:Silicates; C086631:mineral trioxide aggregate; D020123:Sirolimus
keywords: Autophagy; microtubule-associated protein 1 light chain 3; mineral trioxide aggregate; osteoclastogenesis