title: Serotonin Inhibits Osteoblast Differentiation and Bone Regeneration in Rats.
abstract: BACKGROUND
  Although increasing evidence indicates that serotonin (SER; 5-hydroxytrypamine [5-HT]) is involved in the regulation of bone metabolism, conflicting data exist regarding whether SER promotes or inhibits osteoblast differentiation and bone formation. Regeneration of functional bone is required for proper osseointegration of dental implants. Noticeably, the use of selective SER reuptake inhibitors was recently associated with the failure of osseointegrated dental implants. The present study examines the direct role of peripheral SER on the regulation of bone regeneration.
  
  
  METHODS
  The effect of SER on osteoblast differentiation and bone regeneration was examined using rat calvarial cell cultures in vitro and a rat critical-sized calvarial defect model in vivo.
  
  
  RESULTS
  Rat calvarial cells expressed SER receptors Htr1 (5-HT1) and Htr2 (5-HT2), which are known to transmit signals in bone cells. In vitro, SER significantly reduced osteogenic differentiation and mineralization of rat calvarial cells with concomitant reduction of osteoblast marker genes including alkaline phosphatase (Alpl), osterix (Sp7), and osteocalcin (Bglap). Histologic and radiologic analyses using the rat critical-sized calvarial defect model revealed that the existence of SER significantly inhibited β-phase tricalcium phosphate-induced bone regeneration.
  
  
  CONCLUSIONS
  Results suggest that SER in the local bone microenvironment might play a negative role in osteoblast differentiation and bone formation in rats.
authors.affiliation: Department of Periodontology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Soon-Shin
authors.initials: SS
authors.lastname: Nam
authors.affiliation: Department of Dental Biomaterials Science, School of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: Jeong Cheol
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, School of Dentistry, Kyungpook National University.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Periodontology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Periodontology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Jae-Mok
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Periodontology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Jo-Young
authors.initials: JY
authors.lastname: Suh
authors.affiliation: Department of Periodontology, Gangneung-Wonju National University College of Dentistry, Gangneung, Korea.
authors.forename: Heung-Sik
authors.initials: HS
authors.lastname: Um
authors.affiliation: Department of Biochemistry, School of Dentistry, Kyungpook National University.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, School of Dentistry, Kyungpook National University.
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Periodontology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Yong-Gun
authors.initials: YG
authors.lastname: Kim
mesh_terms: D000469:Alkaline Phosphatase; D000818:Animals; D001861:Bone Regeneration; D002454:Cell Differentiation; D010006:Osteoblasts; D010012:Osteogenesis; D051381:Rats; D012701:Serotonin; D012886:Skull
chemical_list: D012701:Serotonin; D000469:Alkaline Phosphatase
keywords: Bone regeneration; cell differentiation; osteoblasts; serotonin