Insulin-like growth factor-I induces early osteoblast gene expression in human mesenchymal stem cells.
Human adult mesenchymal stem cells (hMSCs) differentiate into an osteogenic lineage if the appropriate differentiative cues, such as dexamethasone or bone morphogenetic protein 2 (BMP-2), are present. This study was undertaken to determine the role of insulin-like growth factor I (IGFI) in the regulation of early osteoblast differentiation in hMSC. Previous studies have shown that IGF-I, regulates bone formation and remodeling by participating in the differentiation of mature cells of osteoblast lineage. We hypothesized that IGF-I exerted its effects early, but the effects were too subtle to be detected. Therefore, engineered hMSCs to produce IGF-I via adenoviral transfection and used quantitative real-time PCR (qPCR) to assess marker gene expression. Here we show that IGF-I up-regulates Type I collagen, Runx2, and alkaline phosphatase (Alp) gene expression in hMSCs, genes indicative of early osteogenic differentiation. We also observed mineral deposition in the absence of dexamethasone (Dex) in hMSC cultures treated with recombinant human BMP-2 after transduction with Ad-IGF-I. In conclusion Igf-I transduction up-regulated markers of osteoblastic differentiation and in conjunction with recombinant BMP-2-induced matrix mineralization independently of Dex (see Salasznyk et al., Stem Cells Dev 14(6):608-620, 2005, this issue).
Koch
Hannjörg
H
Department of Orthopaedic Surgery, University of Greifswald, Greifswald, Germany.
Jadlowiec
Julie A
JA
Campbell
Phil G
PG
D000256:Adenoviridae; D000880:Anthraquinones; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D054425:Chemokine CCL27; D019742:Chemokines, CC / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis; D016133:Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000880:Anthraquinones; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C492276:CCL27 protein, human; D054425:Chemokine CCL27; D019742:Chemokines, CC; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D016212:Transforming Growth Factor beta; C010078:alizarin; D007334:Insulin-Like Growth Factor I; D002118:Calcium