Roles of injury-induced inflammatory response in regulating bony repair at injured growth plate cartilage

儿童的生长板软骨负责骨延长。由于运动和玩耍的普及，创伤诱导的生长板损伤和随后的骨生长缺陷在儿童中是常见的，其中高达30%的生长板损伤病例导致生长异常，对于生长异常，目前的手术矫正是高度侵入性的并且不是完全有效的。虽然我们知道生长板损伤引起的骨生长缺陷是由受损生长软骨的骨修复引起的，但我们在很大程度上不了解这种骨修复为什么以及如何发生。在开发有效的生物治疗方法之前，了解这种受损生长板的错误骨修复机制将是至关重要的。最近，我们使用幼鼠的损伤模型，发现在损伤的生长板处骨组织形成之前依次是炎症、纤维形成、软骨形成和成骨反应。炎症反应是一个初始事件，我们最近的研究表明，炎症反应招募炎性细胞，并产生重要的分子，可以显着影响随后的纤维形成，软骨形成和成骨事件，导致骨修复受伤的生长板软骨。目前的建议进一步解决炎症反应的作用和这种反应的分子途径，在调节下游骨修复事件。该项目将产生对受损生长板的错误骨修复的新的理解，并将为开发具有成本效益和简单的治疗干预提供有价值的信息，旨在防止骨修复和增强儿童受损生长板的软骨再生。

Children's growth plate cartilage is responsible for bone lengthening. Due to popularity of sports and play, trauma-induced growth plate damage and subsequently bone growth defects are common in children, with up to 30% of growth plate injury cases resulting in growth abnormality, for which the present surgical correction is highly invasive and not fully effective. Although we know that the growth plate injury-induced bone growth defects result from bony repair of the injured growth cartilage, we largely don't understand why and how this bony repair occurs. Understanding mechanisms for this faulty bony repair of injured growth plate will be critical prior to effective biological treatments can be developed. Recently, using an injury model in young rats, we found that bony tissue formation at injured growth plate is preceded sequentially by inflammatory, fibrogenic, chondrogenic and osteogenic responses. The inflammatory response is an initial event and our recent studies suggest that inflammatory response recruits inflammatory cells and produces important molecules that could significantly influence subsequent fibrogenic, chondrogenic and osteogenic events leading to the bony repair of the injured growth plate cartilage. The current proposal further addresses roles of the inflammatory response and the molecular pathways of this response in regulating downstream bony repair events. This project will generate novel understanding on the faulty bony repair of injured growth plate, and will provide valuable information for developing cost-effective and simple therapeutic intervention that aims to prevent bony repair and to enhance cartilage regeneration of the injured growth plate in children.