title: Dose- and time-dependent effects of recombinant human bone morphogenetic protein-2 on the osteogenic and adipogenic potentials of alveolar bone-derived stromal cells.
abstract: OBJECTIVE
  Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a well-known growth factor that can induce robust bone formation, and recent studies have shown that rhBMP-2-induced osteogenesis is closely related to adipogenesis. The aim of the present study was to determine the dose- and time-dependent effects of rhBMP-2 on the osteogenic and adipogenic differentiation of human alveolar bone-derived stromal cells (hABCs) in vivo and in vitro.
  
  
  METHODS
  hABCs were isolated and cultured, and then transplanted using a carrier treated either with or without rhBMP-2 (100 μg/mL) into an ectopic subcutaneous mouse model. Comprehensive histologic and histometric analyses were performed after an 8-wk healing period. To further understand the dose-dependent (0, 10, 50, 200, 500 and 1000 ng/mL) and time-dependent (0, 3, 5, 7 and 14 d) effects of rhBMP-2 on osteogenic and adipogenic differentiation, in vitro osteogenic and adipogenic differentiation of hABCs were evaluated, and the expression of related mRNAs, including those for alkaline phosphatase, osteocalcin, bone sialoprotein, peroxisome-proliferator-activated receptor gamma-2 and lipoprotein lipase, were assessed using quantitative RT-PCR.
  
  
  RESULTS
  rhBMP-2 significantly promoted the osteogenic and adipogenic differentiation of hABCs in vivo, and gradually increased both the osteogenic and adipogenic potential in a dose- and time-dependent manner with minimal deviation in vitro. The expression of osteogenesis- and adipogenesis-associated mRNAs were concomitantly up-regulated by rhBMP-2.
  
  
  CONCLUSIONS
  The findings of the present study showed that rhBMP-2 significantly enhanced the adipogenic as well as the osteogenic potential of hABCs in dose- and time-dependent manner. The control of adipogenic differentiation of hABCs should be considered when regenerating the alveolar bone using rhBMP-2.
authors.affiliation: Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Korea.
authors.forename: J-C
authors.initials: JC
authors.lastname: Park
authors.forename: J C
authors.initials: JC
authors.lastname: Kim
authors.forename: B-K
authors.initials: BK
authors.lastname: Kim
authors.forename: K-S
authors.initials: KS
authors.lastname: Cho
authors.forename: G-I
authors.initials: GI
authors.lastname: Im
authors.forename: B-S
authors.initials: BS
authors.lastname: Kim
authors.forename: C-S
authors.initials: CS
authors.lastname: Kim
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000328:Adult; D000469:Alkaline Phosphatase / Q000032:analysis; D000539:Alveolar Process / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000494:pharmacology*; D001861:Bone Regeneration / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006882:Hydroxyapatites / Q000737:chemistry; D058574:Integrin-Binding Sialoprotein / Q000032:analysis; D008071:Lipoprotein Lipase / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D015675:Osteocalcin / Q000032:analysis; D010012:Osteogenesis / Q000187:drug effects*; D047495:PPAR gamma / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects* / Q000637:transplantation; D040521:Subcutaneous Tissue / Q000601:surgery; D013997:Time Factors; D054457:Tissue Scaffolds / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D055396:Bone Morphogenetic Protein 2; D006882:Hydroxyapatites; D058574:Integrin-Binding Sialoprotein; D047495:PPAR gamma; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D015675:Osteocalcin; C094280:hydroxyapatite-tricalciumphosphate composite; D008071:Lipoprotein Lipase; D000469:Alkaline Phosphatase