CRANIAL VS APPENDICULAR SKELETAL REPAIR MECHANISMS

颅骨与附肢骨骼修复机制

• 批准号: 6662812
• 负责人: Jill Helms A Helms
• 金额: $ 12.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6662812
• 关键词: bone morphogenetic proteins; cell cell interaction; chondrocytes; collagenase; connective tissue development; epiphysis; histogenesis; immunocytochemistry; in situ hybridization; laboratory mouse; mandible /maxilla; musculoskeletal regeneration; osteoblasts; skull

Skeletal development requires an exquisite coordination of programs for cell specification, migration, proliferation and differentiation that are regulated by interactions between tissue layers and the extracellular matrix. Many of the same events occur during adult bone repair. However, it is unclear to what extent the process of skeletal healing is a recapitulation of the skeletal development program. The goal of this research is to elucidate the molecular and cellular mechanisms regulating cranial skeletal repair, with a focus on the mandible. The underlying hypothesis is that adult tissues heal by using the fetal skeletogenic program. The following specific aims are propose. (1) Determine the spatial and temporal distribution of key chondrocyte- and osteoblast-specific gene products in the cranial skeleton by histological and molecular means. (2) Determine the mechanisms regulation repair in the mandible. In this aim, bones will be allowed to heal by primary intention (intramembranous ossification), and the expressions and functions of molecules that appear to regulate cranial skeletal tissues will be perturbed. (3) Determine the effects on cranial skeletal tissues of perturbing bone development by genetic and biochemical means. The gelatinase-B null mouse will be used to study the role of gelatinase B in regulation of mandibular bone formation. Gelatinase B mice have abnormal pattern of growth plate ossification due to a delay in angiogenesis. These experiments will assess similarities and differences between mandibular morphogenesis and long bone development. These studies may uncover fundamental differences between formation and repair of cranial skeletal tissues, or between the repair of cranial skeletal tissues and long bones. The long term goal is to use this information to develop biologically based therapies for the treatments of skeletal deformities and defects cause by trauma and disease.

骨骼发育需要通过组织层与细胞外基质之间相互作用来调节细胞规范，迁移，增殖和分化程序的精美协调。成人骨修复期间发生了许多相同的事件。但是，尚不清楚骨骼愈合的过程在多大程度上是对骨骼发育计划的概括。这项研究的目的是阐明调节颅骨修复的分子和细胞机制，重点是下颌骨。潜在的假设是成年组织通过使用胎儿骨骼发明程序愈合。提出以下特定目标。 （1）通过组织学和分子均值，确定颅骨骨骼中关键软骨细胞和成骨细胞特异性基因产物的空间和时间分布。 （2）确定下颌骨的机理调节修复。在此目标中，将允许骨骼通过主要意图（膜内骨化）愈合，并且似乎调节颅骨骨骼组织的分子的表达和功能将受到干扰。 （3）通过遗传和生化手段确定对骨骼发育的颅骨骨骼组织的影响。明胶酶-b无效小鼠将用于研究明胶酶B在调节下颌骨形成中的作用。由于血管生成延迟，明胶酶B小鼠具有生长板骨化的异常模式。这些实验将评估下颌形态发生和长骨发育之间的相似性和差异。这些研究可能会发现颅骨组织的形成和修复之间的根本差异，或者在颅骨组织的修复和长骨骼之间的修复之间存在根本差异。长期目标是使用这些信息来开发基于生物学的疗法，用于通过创伤和疾病引起的骨骼畸形和缺陷。