Dawson Lindsay A, Yu Ling, Yan Mingquan, Marrero Luis, Schanes Paula P, Dolan Connor, Pela Maegan, Petersen Britta, Han Manjong, Muneoka Ken
Veterinary Physiology and Pharmacology Texas A&M University 4466 TAMU College Station TX USA.
Cell and Molecular Biology Tulane University 2000 Percival Stern Hall, 6400 Freret St New Orleans LA USA.
Regeneration (Oxf). 2017 Aug 20;4(3):140-150. doi: 10.1002/reg2.81. eCollection 2017 Jun.
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.
哺乳动物肢体的再生仅限于远端指尖（即末节指骨，P3）的截肢情况。相邻的骨骼元件，即中节指骨（P2），已成为研究再生失败的模型系统，也是测试旨在增强再生方法的部位。我们报告称，外源性应用骨形态发生蛋白2（BMP2）可刺激在截肢平面远端形成一个短暂的软骨痂，该软骨痂介导了截肢的P2骨的再生。BMP2在P2骨修复的骨膜来源的软骨愈合阶段引发显著的再生反应，但在没有骨膜组织的情况下或在骨痂形成后无法诱导再生。我们提供证据表明，在P2的诱导再生中存在一个时间成分，我们将其定义为“再生窗口”。在此窗口内，截肢损伤后细胞对BMP2产生短暂反应。对愈合的P2残端进行简单的再次损伤可重新启动内源性骨修复，包括骨膜软骨形成，从而重新打开“再生窗口”，进而重新创造一个对外源性BMP2治疗有反应的再生允许环境。
