Dexamethasone modulates BMP-2 effects on mesenchymal stem cells in vitro
Department of Orthopedics and Physical Rehabilitation
Medical Subject Headings
Anti-Inflammatory Agents; Biological Markers; Bone Marrow Cells; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cell Differentiation; Cell Proliferation; Cell Survival; Cells, Cultured; Collagen Type I; Dexamethasone; Drug Combinations; Fluorescent Antibody Technique, Indirect; Gene Expression Regulation; Humans; Immunoenzyme Techniques; Mesenchymal Stem Cells; Osteoblasts; Osteopontin; RANK Ligand; RNA, Messenger; Transforming Growth Factor beta
Orthopedics | Rehabilitation and Therapy
Dexamethasone/ascorbic acid/glycerolphosphate (DAG) and bone morphogenic protein (BMP)-2 are potent agents in cell proliferation and differentiation pathways. This study investigates the in vitro interactions between dexamethasone and BMP-2 for an osteoblastic differentiation of mesenchymal stem cells (MSCs). Bone marrow-derived human MSCs were cultured with DAG (group A), BMP-2 + DAG (group B), and DAG + BMP-2 combined with a porous collagen I/III scaffold (group C). RT-PCR, ELISA, immuncytochemical stainings and flow cytometry analysis served to evaluate the osteogenic-promoting potency of each of the above conditions in terms of cell morphology/viability, antigen presentation, and gene expression. DAG induced collagen I secretion from MSCs, which was further increased by the combination of DAG + BMP-2. In comparison, the collagen scaffold and the control samples showed no significant influence on collagen I secretion of MSCs. DAG stimulation of MSCs led also to a steady but not significant increase of BMP-2 level. A DAG and more, a DAG + BMP-2, stimulation increased the number of mesenchymal cells (CD105+/CD73+). All samples showed mRNA of ALP, osteopontin, Runx2, Twist 1 and 2, Notch-1/2, osteonectin, osteocalcin, BSP, and collagen-A1 after 28 days of in vitro culture. Culture media of all samples showed a decrease in Ca(2+) and PO(4) (2-) concentration, whereas a collagen-I-peak only occurred at day 28 in DAG- and DAG + BMP-2-stimulated bone marrow cells. In conclusion, BMP-2 enhances DAG-induced osteogenic differentiation in mesenchymal bone marrow cells. Both agents interact in various ways and can modify osteoblastic bone formation. Inc.
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Citation: J Orthop Res. 2008 Nov;26(11):1440-8. Link to article on publisher's site