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

Estrogen deficiency at the menopause is associated with an increased rate o f bone loss and subsequent risk of skeletal fracture. Whilst cells of the o steoblastic lineage are known to express estrogen receptors, the presence o f estrogen receptors in osteoclasts remains controversial. We have examined expression of the classic estrogen receptor, estrogen receptor-alpha (ER a lpha), during osteoclast differentiation. In situ mRNA hybridisation with a digoxygenin-labelled riboprobe to ER alpha mRNA, together with immunocytoc hemical analysis using a human ER alpha-specific monoclonal antibody demons trated similar findings and confirmed the expression of ER alpha in chondro blasts and osteoblasts from human fetal bone and mineralising human bone ma rrow cultures. ER alpha expression was detected in human bone marrow cultur es treated with 1,25(OH)(2)D-3 and macrophage colony-stimulating factor and in macrophage cultures treated with 1,25(OH)(2)D-3. However, in an in vitr o model of human osteoclast formation, no ER alpha expression was observed in the osteoclasts that developed, The human preosteoclast TCG 51 cell line showed strong expression of ER alpha in contrast to the low levels observe d in the more mature bone resorptive TCG 23 cell line. No expression was de tectable in osteoclasts cultured from giant cell tumour of bone (GCTB) tiss ue or in osteoclasts in Pagetic, GCTB, or hyperparathyroid bone tissues. In conclusion, preosteoclasts express detectable levels of ER alpha, but oste oclast maturation and bone resorption is associated with loss of ER alpha e xpression. This indicates that ER alpha expression and regulation may play a role in osteoclast formation.