Heterotopic bone from stem cells in peripheral nerves released by neurogenic infl

描述（由申请方提供）：异位骨化（HO）或非骨骼部位的骨形成非常罕见，但可能发生在中枢神经系统（CNS）损伤或截肢/髋关节置换术（其中骨骼骨被移除或置换）的病例中。然而，我们自己的数据表明，外周神经也可能有助于这一过程。我们最近发现神经源性炎症介质P物质和CGRP的释放导致肥大细胞的募集和脱粒以及神经重塑。这种重塑涉及神经相关细胞的扩张，以及它们在软组织中的释放和迁移。我们观察了成骨蛋白osterix、棕色脂肪细胞蛋白UCP 1以及原始干细胞因子Klf 4和nanog的表达。这些数据共同使我们假设外周神经具有祖细胞/干细胞，其响应于BMP 2而扩增，以促进新形成的异位骨。然而，这些干/祖细胞的确切性质和起源尚不清楚。我们自己的数据表明，p75阳性细胞要么是祖细胞，要么可能是去分化的雪旺细胞，进行成骨。我们设计了一系列的目标，以分离和表征这些细胞，并证明其功能的贡献，直接或间接异位骨化。

DESCRIPTION (provided by applicant): Heterotopic ossification (HO) or bone formation in non-skeletal sites is very rare but can occur in cases of central nervous system (CNS) inhury or amputation/hip replacement surgery where skeletal bone is removed or replaced. However, our own data suggests that peripheral nerves may also be contributing to this process. We recently showed that release of neurogenic inflammatory mediator's substance P and CGRP, led to recruitment and degranulation of mast cells and nerve remodeling. This remodeling involved expansion of nerve associated cells, as well as their release and migration in the soft tissues. We observed the expression of osteogenic protein osterix, brown adipocyte protein UCP1, and the primitive stem cell factors, Klf4 and nanog. The data collectively have led us to hypothesize that peripheral nerves possess progenitors/stem cells, which expand in response to BMP2 for contribution to the newly forming heterotopic bone. However, the exact nature and origin of these stem/progenitors is unclear. Our own data suggests that p75 positive cells are either progenitor cells, or perhaps de-differentiating Schwann cells, that undergo osteogenesis. We have devised a series of aims to isolate and characterize these cells and demonstrate their functional contribution, either directly or indirectly to heterotopic ossification.