Expression of estrogen receptor-alpha in cells of the osteoclastic lineage

ROC Oreffo, V Kusec, AS Virdi, AM Flanagan… - Histochemistry and cell …, 1999 - Springer
ROC Oreffo, V Kusec, AS Virdi, AM Flanagan, M Grano, A Zambonin-Zallone, JT Triffitt
Histochemistry and cell biology, 1999Springer
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 …
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.
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