title: Pro-Inflammatory Cytokine TNF-α Attenuates BMP9-Induced Osteo/ Odontoblastic Differentiation of the Stem Cells of Dental Apical Papilla (SCAPs).
abstract: OBJECTIVE
  Periapical periodontitis is a common oral disease caused by bacterial invasion of the tooth pulp, which usually leads to local release of pro-inflammatory cytokines and osteolytic lesion. This study is intended to examine the effect of TNF-α on BMP9-induced osteogenic differentiation of the stem cells of dental apical papilla (SCAPs).
  
  
  METHODS
  Rat model of periapical periodontitis was established. TNF-α expression was assessed. Osteogenic markers and ectopic bone formation in iSCAPs were analyzed upon BMP9 and TNF-α treatment.
  
  
  RESULTS
  Periapical periodontitis was successfully established in rat immature permanent teeth with periapical lesions, in which TNF-α was shown to release during the inflammatory phase. BMP9-induced alkaline phosphatase activity, the expression of osteocalcin and osteopontin, and matrix mineralization in iSCAPs were inhibited by TNF-α in a dose-dependent fashion, although increased AdBMP9 partially overcame TNF-α inhibition. Furthermore, high concentration of TNF-α effectively inhibited BMP9-induced ectopic bone formation in vivo.
  
  
  CONCLUSIONS
  TNF-α plays an important role in periapical bone defect during the inflammatory phase and inhibits BMP9-induced osteoblastic differentiation of iSCAPs, which can be partially reversed by high levels of BMP9. Therefore, BMP9 may be further explored as a potent osteogenic factor to improve osteo/odontogenic differentiation in tooth regeneration in chronic inflammation conditions.
authors.affiliation: Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Feilong
authors.initials: F
authors.lastname: Wang
authors.affiliation: Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Huang
authors.affiliation: Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Luo
authors.affiliation: Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Fugui
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Pediatric Dentistry, the Affiliated Stomatology Hospital, Chongqing Medical University, Chongqing, China.|Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.
authors.forename: Juhong
authors.initials: J
authors.lastname: Lin
authors.affiliation: Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D002454:Cell Differentiation; D004790:Enzyme Induction; D055427:Growth Differentiation Factor 2 / Q000378:metabolism*; D008297:Male; D009804:Odontoblasts / Q000378:metabolism* / Q000473:pathology; D010485:Periapical Periodontitis / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D055427:Growth Differentiation Factor 2; D014409:Tumor Necrosis Factor-alpha; D000469:Alkaline Phosphatase
keywords: BMP9; Bone regeneration; Dental regeneration; Inflammation; Mesenchymal stem cells; Osteogenesis; Periapical periodontitis; TNF-α