Skeletal homeostasis in tissue-engineered bone
Skeletal homeostasis in tissue-engineered bone
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DOI：
10.1016/s0736-0266(03)00042-1
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发表时间：
2003-09-01
影响因子：
2.8
通讯作者：
Krebsbach, PH
中科院分区：
文献类型：
--
作者：
Schneider, A;Taboas, JM;Krebsbach, PH
组织工程策略，以刺激骨再生可能提供一种替代方法，传统的骨科和颌面外科治疗。在过去的十年中，在开发仿生基质、生长因子、细胞移植和基因递送疗法以支持新骨生长方面取得了重大进展。然而，目前尚不清楚组织工程骨是否能模仿正常骨骼组织对生理信号的反应。在这里，我们报告说，骨形成的分化移植小鼠骨髓基质细胞（BMSCs）响应于全身递送促钙激素。与对照组小鼠相比，暴露于分解代谢剂量甲状旁腺激素（PTH）的小鼠异位听骨中抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞数量增加。相比之下，通过显微计算机断层扫描和组织形态计量学分析，用合成代谢剂量的PTH治疗促进了骨小梁骨量的显著增加。我们的研究结果表明，从移植的骨髓间充质干细胞形成的骨对正常的生理信号有反应，并且可以通过添加全身性合成代谢剂来增强。因为在单个动物中可以产生多个和不同的听小骨，所以这种多功能系统可以用于：（a）阐明骨再生中的细胞/分子机制;（B）研究健康和疾病中骨髓微环境中的细胞与细胞相互作用;和（c）评估调节体内骨转换的成骨剂的功效。(C)2003骨科研究学会。由爱思唯尔有限公司出版。保留所有权利。
Tissue-engineering strategies to stimulate bone regeneration may offer an alternative approach to conventional orthopaedic and maxillofacial surgical therapies. Over the last decade, significant advances have been accomplished in developing biomimetic matrices, growth factors, cell transplantation and gene delivery therapeutics to support new bone growth. However, it is not known if tissue-engineered bone recapitulates the biology of normal skeletal tissue in response to physiologic cues. Here, we report that bone formed by the differentiation of transplanted murine bone marrow stromal cells (BMSCs) responds to a systemically delivered calciotropic hormone. Ectopic ossicles in mice exposed to catabolic doses of parathyroid hormone (PTH) had increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts as compared to control mice. In contrast, treatment with anabolic doses of PTH promoted a marked increase in trabecular bone mass as analyzed by microcomputed tomography and histomorphometry. Our findings demonstrate that bone formed from transplanted BMSCs is responsive to normal physiologic signals, and can be augmented by the addition of a systemic anabolic agent. Because multiple and distinct ossicles can be generated in a single animal, this versatile system may be used to: (a) elucidate cellular/molecular mechanisms in bone regeneration; (b) study cell-to-cell interactions in the bone marrow microenvironment in health and disease; and (c) evaluate the efficacy of osteotropic agents that modulate bone turnover in vivo. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.