Effects of dioxin and estrogen on collagenase-3 in UMR 106-01 osteosarcoma cells

Nicola C. Partridge, Gerald J. Fiacco, Hobart W. Walling, Olga Y. Barmina, John J. Jeffrey, Mary F. Ruh

Research output: Contribution to journalArticlepeer-review

Abstract

Since estrogen is important in preventing osteoporosis in postmenopausal women and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an estrogen antagonist in reproductive tissues, we investigated the effects of 17β-estradiol (E2) and TCDD on collagenase-3 secretion using parathyroid hormone (PTH)-stimulated UMR 106-01 cells, a rat osteoblastic osteosarcoma cell line. Whereas E2 or TCDD had no effect on UMR cells in the absence of PTH, cells grown in the presence of 10-7 M PTH, which induces a dramatic 30-fold increase in collagenase-3 secretion, surprisingly demonstrated a further stimulation of collagenase-3 secretion in the presence of TCDD or E2. However, the potentiating response was biphasic; i.e., at higher concentrations of E2 or TCDD, there was no enhancement of the PTH effect. PTH induces multiple effects on UMR cells, including inducing collagenase-3 mRNA transcription and regulating its extracellular abundance through a specific receptor and endocytosis. Thus, we investigated the ability of TCDD or E2 to stimulate the induction of collagenase-3 mRNA using Northern analysis. As previously reported, PTH dose dependently induced collagenase-3 mRNA after 4 h of treatment. There was little effect of TCDD or E2 on PTH-induced levels of collagenase-3 mRNA. These data could not account for the final effects on secreted collagenase-3. We postulated that low concentrations of E2 and TCDD may downregulate the collagenase-3 endocytotic two-step receptor-mediated process that includes the LDL-receptor-related protein to enhance the effects of PTH. However, this was not the case. Therefore, we conclude that low concentrations of TCDD and estrogen alter translation or secretion of PTH-stimulated collagenase-3. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)182-188
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume382
Issue number2
DOIs
StatePublished - Oct 15 2000

Keywords

  • Collagenase-3
  • Dioxin
  • Estrogen
  • Osteoblasts
  • Parathyroid hormone

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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