TYPE-I PROCOLLAGEN SYNTHESIS IS REGULATED BY STEROIDS AND RELATED HORMONES IN HUMAN OSTEOSARCOMA CELLS

Citation
A. Mahonen et al., TYPE-I PROCOLLAGEN SYNTHESIS IS REGULATED BY STEROIDS AND RELATED HORMONES IN HUMAN OSTEOSARCOMA CELLS, Journal of cellular biochemistry, 68(2), 1998, pp. 151-163
Citations number
65
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Cell Biology
ISSN journal
0730-2312
Volume
68
Issue
2
Year of publication
1998
Pages
151 - 163
Database
ISI
SICI code
0730-2312(1998)68:2<151:TPSIRB>2.0.ZU;2-8
Abstract
Changes in the synthesis of type I collagen, the major extracellular m atrix component of skin and bone, are associated with normal growth, t issue repair processes, and several pathological conditions. Expressio n of the COL1A1 gene is regulated by transcriptional and post-transcri ptional mechanisms. However, the hormonal regulation of type collagen synthesis in human bone has not been well characterized. We have studi ed the influence of calcitriol, dexamethasone, retinoic acid, and estr adiol on the COL1A1 gene expression by determining the secretion of th e C-terminal propeptide (PICP) and the levels of alpha 1(I) procollage n mRNA in cultured human MG-63 and SaOs-2 osteoblast-like osteosarcoma cells. Similar experiments were also performed with respect to expres sion of the nuclear proto-oncogenes, c-fos and c-jun, in MG-63 cells. In MG-63 cells, calcitriol stimulated the synthesis and secretion of P ICP. The alpha 1(I) procollagen mRNA level was elevated with no effect on message stability, indicating a transcriptional mechanism of regul ation. In contrast, dexamethasone treatment was accompanied by an acce lerated rate of alpha 1(I) procollagen mRNA turnover, observed as decr eased amounts of the message and the secreted PICP, implying a posttra nscriptional regulation. Retinoic acid, in turn, decreased the levels of alpha 1(I) procollagen mRNA and secreted PICP by slowing down trans cription of the COL1A1 gene without any effect on message stability. T he ability of these hormones to regulate the alpha 1(I) transcripts wa s sensitive to puromycin treatment, suggesting an involvement of an in duced mediator protein in the action of the hormones on the COL1A1 gen e. Both dexamethasone and calcitriol rapidly but transiently increased the expression of the c-fos and c-jun proto-oncogenes. Neither proto- oncogene responded to retinoic acid treatment with significant changes in mRNA levels. Estradiol treatment was found to have no influence on type I procollagen synthesis. In SaOs-2 cells, which are not as well differentiated as the MG-63 cells, calcitriol and dexamethasone did no t influence type I procollagen synthesis. Retinoic acid as well as est radiol reduced collagen gene expression in these cells.These findings suggest that hormonal effects on type I procollagen synthesis may depe nd on the maturational slate of the osteoblastic cells that express di fferent regulatory factors and receptors, resulting in, in each case, a finely adjusted rate of gene expression. (C) 1998 Wiley-Liss, Inc.