title: Periodontitis mainly increases osteoclast formation via enhancing the differentiation of quiescent osteoclast precursors into osteoclasts.
abstract: OBJECTIVE
  Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts are formed in sequential steps: proliferation and differentiation of hematopoietic progenitors into quiescent osteoclast precursors (QOPs), followed by fusion of QOPs. In this study, we investigated whether enhancement of osteoclast formation by periodontitis is derived from the stimulation of proliferation of hematopoietic progenitors or the differentiation of QOPs into osteoclasts.
  
  
  METHODS
  Ligatures were placed around the first molars in the left mandibles of Fischer 344 inbred rats. The rats received drinking water containing bromodeoxyuridine (BrdU) (which can be incorporated into dividing nuclei) after ligation during the experimental period. The number of inflammatory cells in the distal area was counted. Alveolar bone loss was histologically estimated by measuring the distance from the cementoenamel junction to the alveolar bone crest in the distal area and determining the percentage of periodontal ligament area in the furcation. The number of osteoclasts and percentage of BrdU(+) nuclei in total osteoclasts nuclei were counted after TRAP and BrdU double labeling.
  
  
  RESULTS
  The number of polymorphonuclear cells increased on day 1 and then rapidly decreased. The number of mononuclear cells increased in a time-dependent manner up to day 5 and remained the same until day 10. Alveolar bone loss of ligatured teeth increased in a time-dependent manner. The number of osteoclasts peaked on day 3 then gradually decreased. At peak, the percentage of BrdU(+) nuclei in total osteoclasts nuclei in the distal and furcation areas were 7.9% and 4.1%, respectively.
  
  
  CONCLUSIONS
  These results indicate that most of the osteoclasts formed after periodontitis induction are derived from preformed QOPs, suggesting that enhancement of osteoclast formation by periodontitis might be mainly caused by stimulating the differentiation of QOPs into osteoclasts.
authors.affiliation: Department of Oral Biology, College of Dentistry, Yonsei University, Seoul, South Korea; Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, South Korea; Brain Korea 21 Plus Project, College of Dentistry, Yonsei University, Seoul, South Korea.
authors.forename: D-E
authors.initials: DE
authors.lastname: Lee
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.forename: S-H
authors.initials: SH
authors.lastname: Choi
authors.forename: J-H
authors.initials: JH
authors.lastname: Cha
authors.forename: E-J
authors.initials: EJ
authors.lastname: Bak
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Yoo
mesh_terms: D016301:Alveolar Bone Loss / Q000473:pathology; D000539:Alveolar Process / Q000473:pathology; D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D002467:Cell Nucleus / Q000473:pathology; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology / Q000502:physiology*; D010518:Periodontitis / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000502:physiology*; D000071681:Tartrate-Resistant Acid Phosphatase / Q000032:analysis; D013997:Time Factors; D019237:Tooth Cervix / Q000473:pathology
chemical_list: D000071681:Tartrate-Resistant Acid Phosphatase; D001973:Bromodeoxyuridine
keywords: differentiation; osteoclasts; periodontitis; quiescent osteoclast precursors