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

神经源性感染释放的周围神经干细胞的异位骨

基本信息

批准号：
8499272
负责人：
Alan ROBERT Davis
金额：
$ 16.73万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8499272
关键词：
Adipocytes Amputation Aortic Diseases Area BMP2 gene Blood Vessels Bone Morphogenetic Proteins Bone Tissue Bone plates Burn injury Cartilage Cells Characteristics Chickens Clinical Coin Coronary Cromoglicic Acid Data Development Diagnostic Disease Embryo Environment Epiphysial cartilage Foundations Fracture Hereditary Disease Heterotopic Ossification Homeostasis Immigration Immunofluorescence Microscopy In Vitro Inflammation Inflammation Mediators Injury Knowledge Laboratories Light Link Maintenance Medicine Modeling Molecular Mus Nature Nerve Neural Crest Neuraxis Neurofibromatoses Neurologic Operative Surgical Procedures Osteoblasts Osteogenesis Osteoporosis Patients Peripheral Nerves Phenotype Play Population Process Proteins Regulation Reporter Research Resources Schwann Cells Series Signal Transduction Site Skeletal bone Skeleton Source Stem Cell Factor Stem cells Structure Substance P System Tamoxifen Testing Time Tissue Engineering Tissues Trauma Traumatic Brain Injury Work afferent nerve bone bone morphogenetic protein 7 calcification design early onset high risk hip replacement arthroplasty in vivo insight mast cell novel osteogenic osteogenic protein preference progenitor progressive myositis ossificans relating to nervous system repaired response rib bone structure skeletal soft tissue spine bone structure stem transcriptional coactivator p75 tumor

项目摘要

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.

描述（由申请人提供）：非骨骼部位的异位骨化（HO）或骨形成非常罕见，但在中枢神经系统（CNS）inhury或截肢/髋关节置换手术的情况下可能发生，在这些情况下，去除或替换了骨骼骨骼。但是，我们自己的数据表明，周围神经也可能导致这一过程。我们最近表明，神经发生炎症介质的物质P和CGRP的释放导致肥大细胞和神经重塑的募集和脱粒。这种重塑涉及神经相关细胞的扩展及其在软组织中的释放和迁移。我们观察到成骨蛋白Osterix，棕色脂肪细胞蛋白UCP1以及原始干细胞因子KLF4和Nanog的表达。该数据统称使我们假设外周神经具有祖/干细胞，这些神经是对BMP2的响应而扩展的，以贡献新形成的异位骨。但是，这些茎/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，要么是脱牙细胞，即进行成骨的细胞。我们已经设计了一系列的目标，以隔离和表征这些细胞，并直接或间接地表现出它们的功能贡献。