uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Experimental studies on the effects of insulin-like growth factor I and glucocorticoids on bone metabolism
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
1998 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Osteoporosis is a major cause of disability among patients that are dependent on glucocorticoids in the treatment of inflammatory disease. The pathogenesis behind this side effect is complex, involving dysregulation of hormonal systems and direct effects on bone cells. The present thesis investigates the effects of glucocorticoids on the cells of the skeleton; the osteoblasts and the osteoclasts. First, three techniques for the isolation and culture of human osteoblast-like cells were compared and differences in the expression of markers of the osteoblastic phenotype were described. Also, a new fluorometric assay for the quantification of osteoblast cell proliferation was optimised and found to measure cell number in an accurate and reliable manner. Two main experimental in vitro models were used; primary isolations of human osteoblast-like cells (hOB) and a bone resorption assay based on radioactively labelled neonatal mouse calvariae. Specific focus was on the ability of insulin-like growth factor I (IGF-I) and growth hormone (GH) to modulate the effects of glucocorticoids on production of matrix proteins in the hOB system and the effect on osteoclast activity in the resorption assay.

This thesis shows that dexamethasone inhibits proliferation of hOB cells when applied at doses above 0.1 µM and that both collagen type I and osteocalcin secretion is potently inhibited. Co-treatment with IGF-I totally reversed the inhibition of hydrocortisone on collagen synthesis but could only partially reverse the inhibitory effect of dexamethasone on cell growth. IGF-I, but not GH, stimulated osteocalcin secretion in the presence of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and right shifted the dose-response curve of dexamethasone-induced inhibition of osteocalcin secretion. This effect may be mediated through an increased number of vitamin D receptors (VDR), since IGF-I increased VDR mRNA levels in the MG63 osteosarcoma cell line. Furthermore, it is shown that, although IGF-I stimulated the formation of osteoclasts in murine bone marrow cultures, it did not enhance bone resorption in neonatal mouse calvariae. Instead, IGF-I inhibited parathyroid hormone-, 1,25(OH)2D3-, prostaglandin E2- and dexamethasone-induced bone resorption. In summary, IGF-I counteracts the negative effects of glucocorticoids on bone cells and might be beneficial in the treatment of glucocorticoid-induced osteoporosis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1998. , 44 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 745
Keyword [en]
Medical sciences, Bone, bone resorption, glucocorticoids, insulin-like growth factor I, osteoblasts
Keyword [sv]
National Category
Medical and Health Sciences
Research subject
URN: urn:nbn:se:uu:diva-148ISBN: 91-554-4157-2OAI: oai:DiVA.org:uu-148DiVA: diva2:161045
Public defence
1998-04-16, Grönwallsalen, Akademiska sjukhuset, ingång 70, Uppsala, Uppsala, 09:15
Available from: 1998-03-26 Created: 1998-03-26Bibliographically approved

Open Access in DiVA

No full text
Buy this publication >>

By organisation
Department of Medical Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 144 hits
ReferencesLink to record
Permanent link

Direct link