Enhanced adipogenic differentiation and reduced collagen synthesis induced by hPDLSCs might underlie the negative effect of rhBMP-2 on periodontal regeneration

Abstract

Background and objective: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a potent inducer for regeneration of mineralized tissue, but with limited effect on the regeneration of cementum and periodontal ligaments (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.Materials and Methods: hPDLSCs were isolated and cultured, and then transplanted using a carrier treated either with or without rhBMP-2 into an ectopic subcutaneous mouse model. Comprehensive histologic, histometric, and immunohistochemical analyses were performed after an 8-week of 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 mRNA and protein expressions of collagen types I, II, III, and V were 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 profile.Conclusion: In summary, the findings of the present study suggest that enhanced adipogenic differentiation and inhibition of collagen synthesis by hPDLSCs appear responsible in part for the minimal effect of rhBMP-2 on cementum and PDL tissue regeneration by hPDLSCs.