Dexamethsone suppresses bone formation via the osteoclast.
Dexamethsone suppresses bone formation via the osteoclast.
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DOI：
10.1007/978-0-387-72009-8_5
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发表时间：
2007
影响因子：
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通讯作者：
Hyun-Ju Kim;Haibo Zhao;H. Kitaura;Sandip Bhattacharyya;J. Brewer;L. Muglia;F. Ross;S. Teitelbaum
中科院分区：
文献类型：
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作者：
Hyun-Ju Kim;Haibo Zhao;H. Kitaura;Sandip Bhattacharyya;J. Brewer;L. Muglia;F. Ross;S. Teitelbaum
糖皮质激素是治疗炎症和免疫疾病的核心。然而，这些类固醇深刻地影响骨骼，特别是当长时间服用时。事实上，高剂量糖皮质激素治疗几乎普遍与骨质流失有关，导致最常见的严重骨质疏松症。尽管糖皮质激素诱导的骨质疏松症的发生率和严重程度都很高，但其治疗效果并不令人满意，这表明其发病机制尚未完全了解。净骨量代表了成骨细胞和破骨细胞的相对活性，毫无疑问，糖皮质激素通过加速凋亡抑制体内骨形成细胞（Weinstein 2001; Weinstein，Jilka，Parfitt，et al. 1998）。然而，令人惊讶的是，向骨祖细胞培养物中添加糖皮质激素实际上增加了它们形成矿化骨结节的能力（奥宾1999; Purpura，奥宾，and Zandstra 2004）。这一悖论提出了一种可能性，即糖皮质激素抑制骨形成，在体内，至少部分地反映了类固醇的靶向中间细胞，这反过来又抑制成骨细胞。骨重建是一个不断发生的事件，在哺乳动物中，其特征是破骨细胞和成骨细胞功能的束缚。这个过程是由破骨细胞（OC）吸收一包骨，这反过来又导致成骨细胞被招募到吸收部位开始的。这一过程表明，成骨细胞骨吸收以某种方式促进同一部位的成骨细胞骨形成。因此，病理学或药理学抑制的再吸收会导致成骨细胞活性停滞。
Glucocorticoids are central to treating inflammatory and immune disorders. These steroids, however, profoundly impact the skeleton, particularly when administered for prolonged periods. In fact, high-dose glucocorticoid therapy is almost universally associated with bone loss, prompting among the most common forms of crippling osteoporosis. Despite the frequency and severity of glucocorticoid-induced osteoporosis, its treatment is less than satisfactory, suggesting that its pathogenesis is incompletely understood.Net bone mass represents the relative activities of osteoblasts and osteoclasts and there is little question that glucocorticoids suppress the bone-forming cells, in vivo, via a process involving accelerated apoptosis (Weinstein 2001; Weinstein, Jilka, Parfitt, et al. 1998). Surprisingly, however, addition of glucocorticoids to cultures of osteoprogenitor cells actually increases their capacity to form mineralized bone nodules (Aubin 1999; Purpura, Aubin, and Zandstra 2004). This paradox raises the possibility that glucocorticoid suppression of bone formation, in vivo, reflects, at least in part, the steroid’s targeting intermediary cells, which in turn inhibit the osteoblast.Bone remodeling is an ever-occuring event in mammals which is characterized by tethering of osteoclast and osteoblast function. The process is initiated by osteoclasts (OCs) resorbing a packet of bone, which in turn leads to osteoblasts being recruited to the site of resorption. This process establishes that osteoclastic bone resorption, in some manner, promotes osteoblastic bone formation at the same location. Consequently, pathologically or pharmacologically inhibited resorption eventuates in arrested osteoblast activity.