Park J‐C, Kim J.C, Kim B‐K, Cho K‐S, Im G‐I, Kim B‐S, Kim C‐S. Dose‐ and time‐dependent effects of recombinant human bone morphogenetic protein‐2 on the osteogenic and adipogenic potentials of alveolar bone‐derived stromal cells. J Periodont Res 2012; 47: 645–654. © 2012 John Wiley & Sons A/S Background and 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. Material and 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. Conclusion: 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.
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