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Enhanced adipogenic differentiation and reduced collagen synthesis induced by human periodontal ligament stem cells might underlie the negative effect of recombinant human bone morphogenetic protein-2 on periodontal regeneration.

 D-S. Song  ;  J-C. Park  ;  I-H. Jung  ;  S-H. Choi  ;  K-S. Cho  ;  C-K. Kim  ;  C-S. Kim 
 JOURNAL OF PERIODONTAL RESEARCH, Vol.46(2) : 193-203, 2011 
Journal Title
Issue Date
Adipogenesis/drug effects* ; Adipogenesis/physiology ; Adolescent ; Animals ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins/pharmacology* ; Bone and Bones/anatomy & histology ; Cell Culture Techniques ; Cell Differentiation/drug effects ; Cementogenesis/drug effects ; Collagen/biosynthesis ; Collagen/drug effects* ; Collagen Type I/drug effects ; Collagen Type II/drug effects ; Collagen Type III/drug effects ; Collagen Type V/drug effects ; Dental Cementum/anatomy & histology ; Dose-Response Relationship, Drug ; Down-Regulation ; Humans ; Mice ; Osteogenesis/drug effects ; Periodontal Ligament/cytology* ; Periodontal Ligament/drug effects ; Recombinant Proteins/pharmacology* ; Regeneration/drug effects ; Stem Cell Transplantation ; Stem Cells/drug effects* ; Stem Cells/physiology ; Subcutaneous Tissue/surgery ; Time Factors ; Tissue Scaffolds ; Transforming Growth Factor beta/pharmacology* ; Young Adult
recombinant human human bone morphogenetic protein‐2 ; periodontal regeneration ; cementum ; collagen ; adipogenic differentiation ; osteogenic differentiation
BACKGROUND AND OBJECTIVE: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a potent inducer for the regeneration of mineralized tissue, but has a limited effect on the regeneration of cementum and periodontal ligament (PDL). The aim of the present study was to determine the effects of rhBMP-2 on the in vitro and in vivo biologic activity of well-characterized human PDL stem cells (hPDLSCs) and to elucidate the underlying mechanism of minimal periodontal regeneration by rhBMP-2.

MATERIAL AND METHODS: hPDLSCs were isolated and cultured, and then transplanted into an ectopic subcutaneous mouse model using a carrier treated either with or without rhBMP-2. Comprehensive histologic, histometric and immunohistochemical analyses were performed after an 8-wk healing period. The effects of rhBMP-2 on the adipogenic and osteogenic/cementogenic differentiation of hPDLSCs were also evaluated. The effect of rhBMP-2 on both soluble and insoluble collagen synthesis was analyzed, and the expression of mRNA and protein for collagen types I, II, III and V was assessed.

RESULTS: In the present study, rhBMP-2 promoted both adipogenic and osteogenic/cementogenic differentiation of hPDLSCs in vitro, and the in vivo potential of hPDLSCs to form mineralized cementum and organized PDL tissue was down-regulated following treatment with rhBMP-2. Collagen synthesis, which plays a crucial role in the regeneration of cementum and the periodontal attachment, was significantly reduced, with associated modification of the relevant mRNA and protein expression profiles.

CONCLUSION: In summary, the findings of the present study suggest that enhanced adipogenic differentiation and inhibition of collagen synthesis by hPDLSCs appear to be partly responsible for the minimal effect of rhBMP-2 on cementum and PDL tissue regeneration by hPDLSCs
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Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Periodontics (치주과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chong Kwan(김종관)
Kim, Chang Sung(김창성) ORCID logo https://orcid.org/0000-0003-3902-1071
Park, Jung Chul(박정철)
Jung, Im Hee(정임희)
Cho, Kyoo Sung(조규성) ORCID logo https://orcid.org/0000-0002-6777-5287
Choi, Seong Ho(최성호) ORCID logo https://orcid.org/0000-0001-6704-6124
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