The localization of the functional glucocorticoid receptor α in human bone
The localization of the functional glucocorticoid receptor α in human bone
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DOI：
10.1210/jc.85.2.883
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发表时间：
2000-02-01
影响因子：
5.8
通讯作者：
Compston, JE
中科院分区：
文献类型：
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作者：
Abu, EO;Horner, A;Compston, JE
糖皮质激素对骨骼的影响已有充分记录，但其作用机制仍知之甚少。糖皮质激素对骨细胞的作用部分是通过特定受体直接介导的。这些受体的存在已在体外啮齿动物和人类成骨细胞中得到证实，但它们在体内人骨中的存在尚未有报道。在这项研究中，我们使用针对功能性糖皮质激素受体α（GRα）的特异性亲和纯化多克隆抗体，使用新生儿肋骨、颅骨和椎骨、青少年胫骨生长板和成人髂嵴活检切片来研究其在发育中和成人骨骼中的表达。在胫骨生长板中，GRα主要在软骨内的肥大软骨细胞中表达。在原发性海绵体内，该受体在骨模型部位的成骨细胞中高度表达。在骨髓内，还在单核细胞和血管内皮细胞中检测到受体。在新生儿肋骨和椎骨中，GRα广泛分布于静息、增殖、成熟和肥大软骨细胞的软骨内骨形成部位。它们在骨建模部位的成骨细胞中也高度表达。在新生儿颅骨和肋骨骨膜的膜内骨化部位，GRa在纤维组织内的细胞以及成骨表面和建模部位的成骨细胞中广泛表达。在成人的髂嵴中，GR α 主要在骨细胞中表达。在破骨细胞中未检测到受体。我们的结果首次表明，人骨中存在功能性 GR α 原位，并表明糖皮质激素对骨的作用可能部分是通过生命不同阶段的 GR 直接介导的。破骨细胞中受体表达的缺失也表明糖皮质激素对骨吸收的影响可能是间接介导的。
Glucocorticoids have well-documented effects on the skeleton, although their mechanism of action is still poorly understood. The actions of glucocorticoids on bone cells are mediated, in part, directly via specific receptors. The presence of these receptors has been demonstrated in both rodent and human osteoblastic cells in vitro, but their presence in human bone in vivo has not been reported.In this study, we have used specific affinity purified polyclonal antibodies to the functional glucocorticoid receptor alpha (GR alpha) to investigate its expression in both developing and adult human bone using sections of neonatal rib, calvarial, and vertebral bones, tibial growth plates from adolescents, and iliac crest biopsies from adults who were to undergo liver transplantation.In the tibial growth plates, GR alpha was predominantly expressed in the hypertrophic chondrocytes within the cartilage. In the primary spongiosa, the receptor was highly expressed by osteoblasts at sites of bone modeling. Within the bone marrow, receptors were also detected in mononuclear cells and in endothelial cells of blood vessels. In the neonatal rib and vertebrae, GR alpha was widely distributed at sites of endochondral bone formation in resting, proliferating, mature, and hypertrophic chondrocytes. They were also highly expressed in osteoblasts at sites of bone modeling. At sites of intramembranous ossification in neonatal calvarial bone and rib periosteum, GRa was widely expressed in cells within the fibrous tissue and in osteoblasts at both the bone-forming surface and at modeling sites. In the iliac crests from adults, GR alpha was predominantly expressed in osteocytes. The receptors were not detected in osteoclasts.Our results show for the first time the presence of the functional GR alpha in human bone in situ and suggest that the actions of glucocorticoids an bone may be mediated, in part, directly via the GR at different stages of life. The absence of receptor expression in osteoclasts also suggests that the effects of glucocorticoids on bone resorption may be mediated indirectly.