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Title: Enhanced osteoblast proliferation and collagen gene expression by estradiol

Estrogens play a crucial role in the development of postmenopausal osteoporosis. However, the mechanism by which estrogens exert their effects on bone is unknown. To examine possible direct effects of 17{beta}-estradiol on bone-forming cells, the authors used pure rat osteoblast-like cells in vitro as a model. Osteoblast-like cells prepared from calvaria of newborn rats were cultured serum-free in methylcellulose-containing medium for 21 days. Osteoblast-like cells proliferate selectively into clonally derived cell clusters of spherical morphorlogy. 17{beta}-Estradiol at concentrations of 0.1 nM and 1 nM enhanced osteoblast-like cell proliferation by 41% and 68% above vehicle-treated controls. The biologically inactive stereoisomer 17{alpha}-estradiol (same concentrations) had no effect. Moreover, the antiestrogen tamoxifen abolished the stimulation of osteoblast-like cell proliferation by 17{beta}-estradiol. After 21 days of culture, RNA was prepared and analyzed in a dot-hybridization assay for the abundance of pro{alpha}1(I) collagen mRNA. Steady-state mRNA levels were increased in cultures treated with 17{beta}-estradiol in a dose-dependent manner with maximal stimulation at 1 nM and 10 nM. At the same concentrations, the percentage of synthesized protein (labeled by ({sup 3}H)proline pulse) that was digestible by collagenase was increased, indicating that 17{beta}-estradiol acts as pretranslational levels to enhance synthesis of bone collagen. These data show thatmore » the osteoblast is a direct target for 17{beta}-estradiol.« less
Authors:
; ;  [1]
  1. (University Hospital of Zurich (Switzerland))
Publication Date:
OSTI Identifier:
6827888
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA); Journal Volume: 85:7
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; BONE CELLS; CELL PROLIFERATION; COLLAGEN; GENE REGULATION; ESTRADIOL; BIOCHEMISTRY; OSTEOPOROSIS; PATHOGENESIS; CELL CULTURES; GROWTH; HYBRIDIZATION; NEONATES; PHOSPHORUS 32; PROLINE; RATS; TRITIUM COMPOUNDS; AMINES; AMINO ACIDS; ANIMAL CELLS; ANIMALS; AZOLES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; CARBOXYLIC ACIDS; CHEMISTRY; CONNECTIVE TISSUE CELLS; DAYS LIVING RADIOISOTOPES; DISEASES; ESTRANES; ESTROGENS; HETEROCYCLIC ACIDS; HETEROCYCLIC COMPOUNDS; HORMONES; HYDROGEN COMPOUNDS; HYDROXY COMPOUNDS; ISOTOPES; LIGHT NUCLEI; MAMMALS; NUCLEI; ODD-ODD NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PHOSPHORUS ISOTOPES; PROTEINS; PYRROLES; PYRROLIDINES; RADIOISOTOPES; RODENTS; SCLEROPROTEINS; SKELETAL DISEASES; SOMATIC CELLS; STEROID HORMONES; STEROIDS; VERTEBRATES 550301* -- Cytology-- Tracer Techniques