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Bone morphogenetic protein-7 (OP1) and transforming growth factor-beta1 modulate 1,25(OH)2-vitamin D3-induced differentiation of human osteoblasts
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
2002 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 275, no 1, 132-142 p.Article in journal (Refereed) Published
Abstract [en]

Bone morphogenetic proteins (BMPs) and transforming growth factor-beta (TGFbeta) are potent regulators of osteoblast differentiation and proliferation, processes that are crucial in bone remodeling. BMPs and TGFbeta act in concert with other local factors and hormones, among them 1,25(OH)2-vitamin D3 and insulin. Here we show that BMP7 inhibits 1,25(OH)2-vitamin D3-induced differentiation of human osteoblasts, whereas TGFbeta1 stimulates it, as assessed by assays for alkaline phosphatase (ALP) induction, matrix mineralization, and morphology changes. BMP7 or TGFbeta1 alone affects the differentiation of human osteoblasts. Similar results were obtained in assays for ALP induction using conditionally immortalized human osteoblasts (hFOB) and primary osteoblasts obtained from trabecular bone of the femoral head after hip replacement surgery. BMP7 stimulation led to a decrease of 1,25(OH)2-vitamin D3-induced binding of nuclear proteins to a vitamin D response element, as shown by electrophoretic mobility shift assay. Our results suggest that 1,25(OH)2-vitamin D3 modulates in opposite ways the effects of BMP7 and TGFbeta1 on osteoblast differentiation.

Place, publisher, year, edition, pages
2002. Vol. 275, no 1, 132-142 p.
Keyword [en]
Bone Morphogenetic Proteins/*pharmacology, Cell Differentiation/*drug effects, Cell Division/drug effects, Cell Line, Cholecalciferol/*pharmacology, Dose-Response Relationship; Drug, Drug Synergism, Enzyme Induction, Humans, Insulin/pharmacology, Nuclear Proteins/drug effects/metabolism, Osteoblasts/drug effects/enzymology/*metabolism, Plasminogen Activator Inhibitor 1/metabolism, Transforming Growth Factor beta/*pharmacology, Transforming Growth Factor beta1
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-10418DOI: 10.1006/excr.2002.5488PubMedID: 11925111OAI: oai:DiVA.org:uu-10418DiVA: diva2:38186
Available from: 2007-03-22 Created: 2007-03-22 Last updated: 2017-12-11Bibliographically approved

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Heldin, Carl-HenrikSouchelnytskyi, Serhiy

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