Aim: To test the hypothesis that genistein stimulates the osteoblastic differentiation through the p38 mitogen activated protein kinase (MAPK)-core-binding factor 1 (Cbfa1) pathway.
Methods: The activation of p38 MAPK was detected by Western blotting. Alkaline phosphatase (ALP) activity and calcium deposition were assessed for osteoblastic differentiation of bone marrow-derived mesenchymal stem cell (BMSC) cultures. The expression of Cbfa1 was analyzed at both the mRNA and protein levels. The activity of Cbfa1 was detected by electrophoretic mobility shift assay. Bone sialoprotein (BSP), ALP, osteocalcin (OC), and osteopontin (OPN) gene transcription were also evaluated by either RT-PCR or Northern blotting.
Results: Genistein (0.01-1 micromol/L) dose dependently led to the rapid and sustained activation of the p38 MAPK pathway in mouse BMSC cultures. Treatment with genistein (1 micromol/L) resulted in increased ALP activity and calcium deposition of BMSC cultures as a function of time. Genistein also enhanced Cbfa1 DNA binding activity and promoted the expressions of Cbfa1 itself as well as several Cbfa1-regulated genes, including ALP, BSP, OC, and OPN. Concurrent treatment with p38 MAPK inhibitor (SB203580) diminished the genistein-induced osteoblastic maturation and p38 MAPK-Cbfa1 activation in mouse BMSC cultures.
Conclusion: These results indicated that genistein could stimulate the osteoblastic differentiation of BMSC cultures through the p38 MAPK-Cbfa1 pathway.
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http://dx.doi.org/10.1111/j.1745-7254.2007.00632.x | DOI Listing |
Biomater Res
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Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Magnesium (Mg)-based implants have evolved as a promising innovation in orthopedic trauma surgery, with the potential to revolutionize the treatment of bone diseases, including osteoporotic fractures and bone defects. Available clinical studies mostly show excellent patient outcomes of resorbable Mg-based implants, without the need for subsequent implant removal. However, the occurrence of radiolucent zones around Mg-based implants seems to be a noticeable drawback for a more widespread clinical use.
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The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
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Department of Experimental Medicine, Biotechnology, and Molecular Biology Section, Luigi Vanvitelli Campania University, Naples, Italy.
Mesenchymal stromal cells (MSCs) are a heterogeneous population of non-hematopoietic adult stem cells derived from the embryonic mesoderm. They possess self-renewal and multipotent differentiation capabilities, allowing them to give rise to mesodermal cell types, such as osteoblasts, chondroblasts, and adipocytes, as well as non-mesodermal cells, including neuron-like cells and endothelial cells. MSCs play a vital role in maintaining homeostasis across various tissues by facilitating tissue repair, immune regulation, and inflammatory response balance.
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Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hematopoietic stem cells (HSCs) reside in a milieu that supports their functions, differentiation, and survival. This niche consists of several types of cells, including mesenchymal stem/stromal cells, endothelial cells, osteoblasts, megakaryocytes, macrophages, adipocytes, lymphoid cells, and nerve fibers. The interactions between these cells and HSCs have a role in HSC fate.
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