Cellular Contribution to Bone Healing

细胞对骨愈合的贡献

• 批准号: 7067597
• 负责人: CELINE I COLNOT
• 金额: $ 7.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067597
• 关键词: biological signal transduction; bone; bone development; bone disorder; cell cell interaction; cell differentiation; cellular pathology; embryogenesis; histology; immunocytochemistry; in situ hybridization; laboratory mouse; normal ossification; periosteums; regeneration; stem cells; wound healing

DESCRIPTION (provided by applicant): My long-term goals are to understand the cellular and molecular mechanisms regulating bone formation during skeletogenesis in the embryo and during repair of injured bone in the adult. The adult skeleton has a remarkable potential to heal by forming new bone that is indistinguishable from adjacent, uninjured tissues. Aspects of this adult regenerative process resemble skeletal development during fetal life. However, differences exist between the fetal developmental program and the adult regenerative process, such as the sources of skeletal stem cells. The origins of adult skeletal stem cells and their cellular and molecular contributions to skeletal tissue regeneration remain under appreciated. The goal of the work outlined in this proposal is to assess the extent to which skeletal stem cells residing in the periosteum (the tissue at the outer surface of bone) and endosteum (the tissue at the inner surface of bone) contribute differently to intramembranous and endochondral ossification during bone repair. Aim 1 will compare the mechanisms of bone healing in the periosteum and endosteum, by analyzing the distinct cellular and molecular responses after creating periosteal or endosteal injuries. Aim 2 will develop a new lineage analysis approach in order to determine the cellular contribution of the periosteum and endosteum during healing via intramembranous and endochondral ossification. This approach will be based on bone grafting experiments, which will allow me to distinguish periosteal- and endosteal-derived cells during healing. Aim 3 will assess the extent to which the healing responses of the periosteum and endosteum are intrinsic to each tissue or whether the microenvironment influences cell differentiation. To do so, bone grafts containing periosteal or endosteal stem cells will be ectopically transplanted and the contribution of these stem cells to bone healing will be analyzed. These experiments will be essential to develop new approaches to elucidate the role of osteogenic and chondrogenic factors on different stem cell populations within the bone. This research will have a direct impact on tissue engineering, which aims to use combinations of stem cells with osteoinductive and osteoconductive materials to improve the treatment of delayed fracture healing and bone diseases.

描述（由申请人提供）：我的长期目标是了解胚胎骨骼形成和成人损伤骨修复过程中调节骨形成的细胞和分子机制。成人骨骼具有显著的愈合潜力，可以形成与相邻未受伤组织难以区分的新骨。这个成人再生过程的各个方面类似于胎儿时期的骨骼发育。然而，胎儿发育程序和成人再生过程之间存在差异，例如骨骼干细胞的来源。成人骨骼干细胞的起源及其对骨骼组织再生的细胞和分子贡献仍未得到充分认识。本建议概述的工作目标是评估骨修复过程中存在于骨膜（骨外表面的组织）和内膜（骨内表面的组织）中的骨干细胞对膜内和软骨内成骨的不同贡献程度。