title: Limited but heterogeneous osteogenic response of human bone marrow mesenchymal stem cells to bone morphogenetic protein-2 and serum.
abstract: Although there are numerous reports describing the in vivo bone forming capability of recombinant human bone morphogenetic proteins-2 (rhBMP-2), studies have reported limited effects on human mesenchymal stem cells (hMSCs). However, the reasons for these discrepancies are not well understood. The aim of this study was to investigate the responsiveness of hMSCs to osteoinductive signals, focusing on rhBMP-2 and the effect of serum on that responsiveness. Human MSCs from six donors were analysed. When those cells were treated with osteoinduction medium including dexamethasone (Dex), alkaline phosphatase (ALP) activities increased in all cell lines. On the other hand, rhBMP-2-containing medium failed to increase ALP activity. When five different sera were used for cultivation and induction with rhBMP-2, ALP activities increased in two of them, but not in the others. The expression of BMP-2 antagonist noggin was induced in almost all combinations regardless of the responsiveness to rhBMP-2. On the other hand, the expression of follistatin showed significant variations depending on the serum and cell line. However, the expression did not correlate with the responsiveness to rhBMP-2. The results from this study showed limited but heterogeneous osteogenic response of hMSCs to rhBMP-2 and that the results are affected by the choice of serum. This fact should be concerned for the successful and effective clinical application of rhBMP-2.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Mizuno
authors.forename: Hideki
authors.initials: H
authors.lastname: Agata
authors.forename: Hiroki
authors.initials: H
authors.lastname: Furue
authors.forename: Ayuko
authors.initials: A
authors.lastname: Kimura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Narita
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Watanabe
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ishii
authors.forename: Minoru
authors.initials: M
authors.lastname: Ueda
authors.forename: Arinobu
authors.initials: A
authors.lastname: Tojo
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kagami
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000187:drug effects; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology*; D044967:Serum / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003907:Dexamethasone; D000469:Alkaline Phosphatase