Age-related changes in effects of insulin-like growth factor I on human osteoblast-like cells.
The role of insulin-like growth factor I (IGF-I) in extracellular matrix metabolism was studied in both proliferating and confluent human osteoblast-like cultures derived from donors of different ages. In proliferating cultures, recombinant human (rh)IGF-I was found to increase the incorporation of [3H]thymidine in a dose- and age-dependent manner. To study cell proliferation dynamically, continuous growth curves with and without rhIGF-I were modelled by a modified logistic function. Increasing doses of rhIGF-I decreased the lag time and maximal growth rates, whereas plateau values decreased only at the highest dose (100 ng/ml). In post-proliferative cell strains, rhIGF-I (0.1-100 ng/ml) increased levels of type I collagen, biglycan and decorin, and to a smaller extent fibronectin and thrombospondin, whereas it decreased the levels of hyaluronan and a versican-like proteoglycan when protein and proteoglycan metabolism were followed by steady-state radiolabelling with [3H]proline, [3H]glucosamine or [35S]sulphate. These responses to rhIGF-I were found to be age-dependent, with osteoblast-like cells derived from younger patients being more responsive to rhIGF-I. When extracellular matrix turnover was analysed by pulse-chase experiments, rhIGF-I had no effect. The steady-state levels of collagen, decorin, hyaluronan and a versican-like proteoglycan for bone cells treated with rhIGF-I on day 7 in culture were equivalent to levels of these matrix components in untreated osteoblasts grown for 14 days. These results are consistent with rhIGF-I's altering cellular proliferative capacity and matrix synthesis, causing a change in the osteoblast differentiated state.
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Division of Geriatrics, Department of Medicine, Room 5A-50 JHAAC, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Frazier
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Shapiro
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Fedarko
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D000375:Aging / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology
D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I