Premium
Type I procollagen synthesis is regulated by steroids and related hormones in human osteosarcoma cells
Author(s) -
Mahonen Anitta,
Jukkola Arja,
Risteli Leila,
Risteli Juha,
Mäenpää Pekka H.
Publication year - 1998
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19980201)68:2<151::aid-jcb2>3.0.co;2-u
Subject(s) - procollagen peptidase , retinoic acid , medicine , endocrinology , gene expression , extracellular matrix , osteoblast , calcitriol , messenger rna , secretion , biology , transcriptional regulation , regulation of gene expression , hormone , chemistry , microbiology and biotechnology , gene , biochemistry , vitamin d and neurology , in vitro
Changes in the synthesis of type I collagen, the major extracellular matrix component of skin and bone, are associated with normal growth, tissue repair processes, and several pathological conditions. Expression of the COL 1A1 gene is regulated by transcriptional and post‐transcriptional mechanisms. However, the hormonal regulation of type I collagen synthesis in human bone has not been well characterized. We have studied the influence of calcitriol, dexamethasone, retinoic acid, and estradiol on the COL 1A1 gene expression by determining the secretion of the C‐terminal propeptide (PICP) and the levels of α1(I) procollagen mRNA in cultured human MG‐63 and SaOs‐2 osteoblast‐like osteosarcoma cells. Similar experiments were also performed with respect to expression 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 PICP. The α1(I) procollagen mRNA level was elevated with no effect on message stability, indicating a transcriptional mechanism of regulation. In contrast, dexamethasone treatment was accompanied by an accelerated rate of α1(I) procollagen mRNA turnover, observed as decreased amounts of the message and the secreted PICP, implying a posttranscriptional regulation. Retinoic acid, in turn, decreased the levels of α1(I) procollagen mRNA and secreted PICP by slowing down transcription of the COL1A1 gene without any effect on message stability. The ability of these hormones to regulate the α1(I) transcripts was sensitive to puromycin treatment, suggesting an involvement of an induced mediator protein in the action of the hormones on the COL1A1 gene. 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 not influence type I procollagen synthesis. Retinoic acid as well as estradiol reduced collagen gene expression in these cells. These findings suggest that hormonal effects on type I procollagen synthesis may depend on the maturational state of the osteoblastic cells that express different regulatory factors and receptors, resulting in, in each case, a finely adjusted rate of gene expression. J. Cell. Biochem. 68:151–163, 1998. © 1998 Wiley‐Liss, Inc.