Effects of dioxin and estrogen on collagenase-3 in UMR 106-01 osteosarcoma cells.
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 17beta-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.
Partridge
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NC
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Missouri 63104, USA. partrinc@umdnj.edu
Fiacco
G J
GJ
Walling
H W
HW
Barmina
O Y
OY
Jeffrey
J J
JJ
Ruh
M F
MF
D000818:Animals; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D053509:Matrix Metalloproteinase 13; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D012516:Osteosarcoma / Q000201:enzymology; D010281:Parathyroid Hormone / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism; D014407:Tumor Cells, Cultured
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010281:Parathyroid Hormone; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D004958:Estradiol; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat