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.
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.


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.


CONCLUSIONS
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.
Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, South Korea.
D-S
DS
Song
J-C
JC
Park
I-H
IH
Jung
S-H
SH
Choi
K-S
KS
Cho
C-K
CK
Kim
C-S
CS
Kim
D050156:Adipogenesis / Q000187:drug effects* / Q000502:physiology; D000293:Adolescent; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001842:Bone and Bones / Q000033:anatomy & histology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D025021:Cementogenesis / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects*; D024042:Collagen Type I / Q000187:drug effects; D024043:Collagen Type II / Q000187:drug effects; D024061:Collagen Type III / Q000187:drug effects; D024062:Collagen Type V / Q000187:drug effects; D003739:Dental Cementum / Q000033:anatomy & histology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology* / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology*; D012038:Regeneration / Q000187:drug effects; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D040521:Subcutaneous Tissue / Q000601:surgery; D013997:Time Factors; D054457:Tissue Scaffolds; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D055815:Young Adult
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D024043:Collagen Type II; D024061:Collagen Type III; D024062:Collagen Type V; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen