Expression of estrogen receptor-alpha in cells of the osteoclastic lineage
Expression of estrogen receptor-alpha in cells of the osteoclastic lineage
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DOI：
10.1007/s004180050342
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发表时间：
1999-02-01
影响因子：
2.3
通讯作者：
Triffitt, JT
中科院分区：
文献类型：
--
作者：
Oreffo, ROC;Kusec, V;Triffitt, JT
更年期雌激素缺乏与骨质流失率增加以及随后的骨骼骨折风险有关。虽然已知成骨细胞谱系的细胞表达雌激素受体，但破骨细胞中雌激素受体的存在仍然存在争议。我们检查了破骨细胞分化过程中经典雌激素受体——雌激素受体-α（ERα）的表达。用地高辛标记的核糖核酸探针与 ER α mRNA 进行原位 mRNA 杂交，并使用人 ER α 特异性单克隆抗体进行免疫细胞化学分析，证明了类似的发现，并证实了 ER α 在来自人胎儿骨和矿化人骨髓培养物的成软骨细胞和成骨细胞中的表达。在用 1,25(OH)(2)D(3) 和巨噬细胞集落刺激因子处理的人骨髓培养物以及用 1,25(OH)(2)D(3) 处理的巨噬细胞培养物中检测到 ER α 表达。然而，在人破骨细胞形成的体外模型中，在发育的破骨细胞中没有观察到 ER α 表达。人前破骨细胞 TCG 51 细胞系显示出 ER α 的强表达，而在更成熟的骨吸收 TCG 23 细胞系中观察到的低水平表达相反。在从骨巨细胞瘤 (GCTB) 组织培养的破骨细胞中或在 Pagetic、GCTB 或甲状旁腺功能亢进骨组织中的破骨细胞中未检测到表达。总之，前破骨细胞表达可检测水平的 ER α，但破骨细胞的成熟和骨吸收与 ER α 表达的丧失相关。这表明ERα表达和调节可能在破骨细胞形成中发挥作用。
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 (ER alpha), during osteoclast differentiation. In situ mRNA hybridisation with a digoxygenin-labelled riboprobe to ER alpha mRNA, together with immunocytochemical analysis using a human ER alpha-specific monoclonal antibody demonstrated similar findings and confirmed the expression of ER alpha in chondroblasts and osteoblasts from human fetal bone and mineralising human bone marrow cultures. ER alpha expression was detected in human bone marrow cultures 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 vitro 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 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 ER alpha, but osteoclast maturation and bone resorption is associated with loss of ER alpha expression. This indicates that ER alpha expression and regulation may play a role in osteoclast formation.