| Inhibited anabolic effect of insulin-like growth factor-I on stromal bone marrow cells in endothelial nitric oxide synthase-knockout mice. | |
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MedLine Citation:
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PMID: 15329054 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: Insulin-like growth factor-I (IGF-I), parathyroid hormone (PTH) and PTH-related protein (PTHrP) are hormones that have anabolic effects on bone formation. The aim of this study was to investigate whether production of nitric oxide (NO) is involved in the effect of IGF-I and PTH/PTHrP on osteoblast-like cells. METHODS: Bone marrow stromal cells from adult endothelial nitric oxide synthase (eNOS)-knockout (eNOSKO) mice and wild type (WT) counterparts were cultivated with osteogenic substances. The cells showed an osteoblastic phenotype measured as osteocalcin production and alkaline phosphatase activity. DNA synthesis was measured as [3H] thymidine incorporation in the bone marrow cells and in a human osteosarcoma cell-line (SaOS-2). RESULTS: The stimulatory effect of IGF-I on thymidine incorporation seen in WT animals was absent in eNOSKO mice. Addition of a NO donor to eNOSKO cells recovered the effect of IGF-I on thymidine incorporation. PTH/PTHrP stimulated cell proliferation in both WT and eNOSKO mice. In SaOS-2 cells, incubation with IGF-I together with a NOS inhibitor resulted in an inhibition of the anabolic effect of IGF-I on cell proliferation. CONCLUSIONS: The stimulatory effect of IGF-I on WT cell proliferation was abolished in eNOSKO cells, recovered by an NO donor and inhibited in osteosarcoma cells by a NOS inhibitor. The results indicate that the effect of IGF-I is dependent on NO production. The impaired IGF-I response may contribute to the bone defect formation seen in eNOSKO animals. |
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Authors:
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A Lagumdzija; G Ou; M Petersson; E Bucht; A Gonon; Y Pernow |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Acta physiologica Scandinavica Volume: 182 ISSN: 0001-6772 ISO Abbreviation: Acta Physiol. Scand. Publication Date: 2004 Sep |
Date Detail:
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Created Date: 2004-08-26 Completed Date: 2004-12-20 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370362 Medline TA: Acta Physiol Scand Country: England |
Other Details:
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Languages: eng Pagination: 29-35 Citation Subset: IM |
Affiliation:
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Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Institutet and Karolinska Hospital, Stockholm, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bone Marrow Cells / metabolism, physiology* Cell Division / physiology Cell Line, Tumor Cells, Cultured DNA / biosynthesis Enzyme Inhibitors / pharmacology Insulin-Like Growth Factor I / physiology* Male Mice Mice, Knockout NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide Donors / pharmacology Nitric Oxide Synthase / metabolism* Osteoblasts / metabolism Osteocalcin / biosynthesis Parathyroid Hormone / physiology Parathyroid Hormone-Related Protein / physiology Penicillamine / analogs & derivatives*, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Nitric Oxide Donors; 0/Parathyroid Hormone; 0/Parathyroid Hormone-Related Protein; 0/S-nitro-N-acetylpenicillamine; 104982-03-8/Osteocalcin; 50903-99-6/NG-Nitroarginine Methyl Ester; 52-67-5/Penicillamine; 67763-96-6/Insulin-Like Growth Factor I; 9007-49-2/DNA; EC 1.14.13.39/Nitric Oxide Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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