The role of mast cells in parathyroid bone disease.
The role of mast cells in parathyroid bone disease.
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DOI：
10.1002/jbmr.49
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发表时间：
2010-07
影响因子：
6.2
通讯作者：
Sibonga, Jean D.
中科院分区：
文献类型：
--
作者：
Turner, Russell T.;Iwaniec, Urszula T.;Marley, Kevin;Sibonga, Jean D.
慢性甲状旁腺功能亢进（HPT）是代谢性骨病的常见原因。这些研究探讨了甲状旁腺激素（PTH）升高对骨骼有害作用的细胞和分子机制。甲状旁腺功能亢进患者的骨活检显示甲状旁腺骨病与骨髓肥大细胞数量增加有关。因此，我们在慢性HPT大鼠模型中评估肥大细胞在甲状旁腺骨病病因学中的作用。在大鼠中，成熟的肥大细胞优先位于骨转换部位，并且用甲状旁腺激素治疗后，骨-骨髓界面的肥大细胞数量大大增加。时程研究和采用甲状旁腺相关肽（PTHrP）以及血小板衍生生长因子-A（PDGF-A，曲匹地尔）、kit（格列卫）和PI 3 K（渥曼青霉素）信号传导抑制剂的研究显示，成熟肥大细胞从骨髓向骨表面的再分布先于纤维性骨炎，并与纤维性骨炎相关，纤维性骨炎是甲状旁腺骨病的标志。重要的是，在小鼠骨髓中未观察到成熟肥大细胞。反过来，小鼠对PTH诱导的骨髓纤维化的发展具有抵抗力。这些发现表明肥大细胞可能是治疗代谢性骨病的新靶点。© 2010美国骨与矿物质研究学会。
Chronic hyperparathyroidism (HPT) is a common cause of metabolic bone disease. These studies investigated the underlying cellular and molecular mechanisms responsible for the detrimental actions of elevated parathyroid hormone (PTH) on the skeleton. Bone biopsies from hyperparathyroid patients revealed an association between parathyroid bone disease and increased numbers of bone marrow mast cells. We therefore evaluated the role of mast cells in the etiology of parathyroid bone disease in a rat model for chronic HPT. In rats, mature mast cells were preferentially located at sites undergoing bone turnover, and the number of mast cells at the bone–bone marrow interface was greatly increased following treatment with PTH. Time-course studies and studies employing parathyroid hormone–related peptide (PTHrP), as well as inhibitors of platelet-derived growth factor-A (PDGF-A, trapidil), kit (gleevec), and PI3K (wortmannin) signaling revealed that mature mast cell redistribution from bone marrow to bone surfaces precedes and is associated with osteitis fibrosa, a hallmark of parathyroid bone disease. Importantly, mature mast cells were not observed in the bone marrow of mice. Mice, in turn, were resistant to the development of PTH-induced bone marrow fibrosis. These findings suggest that the mast cell may be a novel target for treatment of metabolic bone disease. © 2010 American Society for Bone and Mineral Research.
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