The periosteal requirement and temporal dynamics of BMP2-induced middle phalanx regeneration in the adult mouse.
The periosteal requirement and temporal dynamics of BMP2-induced middle phalanx regeneration in the adult mouse.
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DOI：
10.1002/reg2.81
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Muneoka K
中科院分区：
文献类型：
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作者：
Dawson LA;Yu L;Yan M;Marrero L;Schanes PP;Dolan C;Pela M;Petersen B;Han M;Muneoka K
哺乳动物肢体的再生仅限于远端趾尖（终末指骨（P3））的截肢。邻近的骨骼元素，中节指骨（P2），已经成为研究再生失败的模型系统，并作为测试旨在促进再生的方法的部位。我们报告说，外源性应用骨形态发生蛋白2（BMP 2）刺激形成一个短暂的软骨愈伤组织远端截肢平面介导的再生截肢P2骨。BMP 2在P2骨修复的骨膜来源的软骨愈合阶段启动显著的再生反应，但在没有骨膜组织的情况下或在骨痂形成后不能诱导再生。我们提供的证据表明，时间的组成部分存在于诱导再生的P2，我们定义为“再生窗口”。在该窗口中，细胞在截肢损伤后对BMP 2短暂响应。愈合的P2残端的简单再损伤可以重新启动内源性骨修复，完成骨膜软骨形成，从而重新打开“再生窗口”，从而重新创建对外源性BMP 2治疗有反应的再生允许环境。
Regeneration of mammalian limbs is restricted to amputation of the distal digit tip, the terminal phalanx (P3). The adjacent skeletal element, the middle phalanx (P2), has emerged as a model system to investigate regenerative failure and as a site to test approaches aimed at enhancing regeneration. We report that exogenous application of bone morphogenetic protein 2 (BMP2) stimulates the formation of a transient cartilaginous callus distal to the amputation plane that mediates the regeneration of the amputated P2 bone. BMP2 initiates a significant regeneration response during the periosteal‐derived cartilaginous healing phase of P2 bone repair, yet fails to induce regeneration in the absence of periosteal tissue, or after boney callus formation. We provide evidence that a temporal component exists in the induced regeneration of P2 that we define as the “regeneration window.” In this window, cells are transiently responsive to BMP2 after the amputation injury. Simple re‐injury of the healed P2 stump acts to reinitiate endogenous bone repair, complete with periosteal chondrogenesis, thus reopening the “regeneration window” and thereby recreating a regeneration‐permissive environment that is responsive to exogenous BMP2 treatment.