Targeted ablation of Osteocytes induces osteoporosis with defective mechanotransduction
Targeted ablation of Osteocytes induces osteoporosis with defective mechanotransduction
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DOI：
10.1016/j.cmet.2007.05.001
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发表时间：
2007-06-01
期刊：
影响因子：
29
通讯作者：
Ikeda, Kyoji
中科院分区：
文献类型：
--
作者：
Tatsumi, Sawako;Ishii, Kiyoaki;Ikeda, Kyoji
骨重塑是由骨表面的破骨细胞和成骨细胞进行的。骨骼内部是一个由大量骨细胞组成的网络，其具体功能仍然是个谜。在这里，我们描述了一种转基因小鼠模型，其中通过白喉毒素（DT）受体的靶向表达在体内实现骨细胞的诱导性和特异性消融。单次注射 DT 后，大约 70%-80% 的骨细胞被杀死，但显然没有成骨细胞被杀死。骨细胞去除小鼠表现出骨质脆弱、皮质内孔隙和微骨折、成骨细胞功能障碍、小梁骨丢失、微观结构恶化和骨髓空间脂肪组织增殖，所有这些都是骨骼老化的标志。引人注目的是，这些“无骨细胞”小鼠能够抵抗卸载引起的骨质流失，这为骨细胞在机械传导中的作用提供了证据。因此，骨细胞代表了骨疾病（例如骨质疏松症）诊断和治疗开发的有吸引力的目标。
Bone remodeling is performed by osteoclasts and osteoblasts at the bone surface. Inside of bone is a network of numerous osteocytes, whose specific function hasremained anenigma. Here we describe a transgenic mouse model in which inducible and specific ablation of osteocytes is achieved in vivo through targeted expression of diphtheria toxin (DT) receptor. Following a single injection of DT, approximately 70%-80% of the osteocytes, but apparently no osteoblasts, were killed. Osteocyte-ablated mice exhibited fragile bone with intracortical porosity and microfractures, osteolblastic dysfunction, and trabecular bone loss with microstructural deterioration and adipose tissue proliferation in the marrow space, all of which are hallmarks of the aging skeleton. Strikingly, these "osteocyte-less" mice were resistant to unloading-induced bone loss, providing evidence for the role of osteocytes in mechano-transduction. Thus, osteocytes represent an attractive target for the development of diagnostics and therapeutics for bone diseases, such as osteoporosis.