Expression of estrogen receptor-alpha in cells of the osteoclastic lineage |
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Authors: | R O C Oreffo V Kusec A S Virdi A M Flanagan M Grano A Zambonin-Zallone J T Triffitt |
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Institution: | (1) MRC Bone Research Laboratory, University of Oxford, Nuffield Department of Orthopaedic Surgery, Oxford, OX3 7LD, UK e-mail: james.triffitt@ndos.ox.ac.uk Tel. +44–1865–227660; Fax: +44–1865–227673, GB;(2) Department of Histopathology, Imperial College School of Medicine, London, W2 1PG, UK, GB;(3) Department of Human Anatomy, University of Bari, Bari, Italy, IT |
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Abstract: | Estrogen deficiency at the menopause is associated with an increased rate of bone loss and subsequent risk of skeletal fracture.
Whilst cells of the osteoblastic lineage are known to express estrogen receptors, the presence of estrogen receptors in osteoclasts
remains controversial. We have examined expression of the classic estrogen receptor, estrogen receptor-alpha (ERα), during
osteoclast differentiation. In situ mRNA hybridisation with a digoxygenin-labelled riboprobe to ERα mRNA, together with immunocytochemical
analysis using a human ERα-specific monoclonal antibody demonstrated similar findings and confirmed the expression of ERα
in chondroblasts and osteoblasts from human fetal bone and mineralising human bone marrow cultures. ERα expression was detected
in human bone marrow cultures treated with 1,25(OH)2D3 and macrophage colony-stimulating factor and in macrophage cultures treated with 1,25(OH)2D3. However, in an in vitro model of human osteoclast formation, no ERα expression was observed in the osteoclasts that developed.
The human preosteoclast TCG 51 cell line showed strong expression of ERα in contrast to the low levels observed in the more
mature bone resorptive TCG 23 cell line. No expression was detectable in osteoclasts cultured from giant cell tumour of bone
(GCTB) tissue or in osteoclasts in Pagetic, GCTB, or hyperparathyroid bone tissues. In conclusion, preosteoclasts express
detectable levels of ERα, but osteoclast maturation and bone resorption is associated with loss of ERα expression. This indicates
that ERα expression and regulation may play a role in osteoclast formation.
Accepted: 4 November 1998 |
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