MECHANICAL FACTORS IN CARTILAGE REPAIR

描述（改编自申请人的摘要）：每年，成千上万的 年轻的成年人遭受关节表面的损伤，这可能导致过早 关节炎，因为关节软骨不愈合。因此，需要一种方法， 软骨的生物修复或再生。长期目标是 我们的工作是通过了解一系列事件如何优化软骨修复， 在新软骨形成（新软骨形成）的调节。于是不 实现，对调节的分子机制的透彻理解 需要软骨形成和修复。组织与组织工程的最新进展 细胞移植为患者提供了希望， 软骨修复未分化的间充质细胞 （软骨细胞前体）检测机械刺激是未知的。虽然 软骨形成随着年龄的增长而减少，很明显， 通过使用机械刺激来增强，例如连续被动 议案研究人员开发了一种独特的器官培养模型， 骨膜外植体在机械环境中悬浮在argarose中。的 该模型的独特特征在于其模拟软骨的体内修复， 从前软骨细胞的增殖和分化， 然后进行矩阵合成。这项拨款提案的目标是利用 这个体外系统分析软骨修复的细胞反应， 利用流体静压的周期性变化， 这被称为动态流体压力（DFP）。项目的具体 目的是（1）确定软骨形成是否需要细胞增殖; (2)表征DFP介导的软骨形成过程中的表型变化;（3） 鉴定骨膜软骨形成过程中DFP作用的介质;和（4） 确定骨膜对DFP反应的年龄相关变化， 初步了解如何以及为什么软骨修复潜力 随着年龄的增长而下降。本文认为，翻译研究是一种新的研究方法， 这种应用是重要的，因为软骨修复技术，例如 骨膜移植，目前用于治疗患者。的结果 这些研究建立了机械刺激的参数， 组织工程软骨和一个框架，进一步的研究和 软骨修复的组织工程可以基于，包括细胞如何 在旁分泌调节过程中相互作用。据认为，这些发现将 与骨科其他重要领域的相关性，包括骨折愈合， 并有可能对患者的护理产生重大影响。

DESCRIPTION (Adapted from the Applicant's Abstract): Each year, thousands of young adults sustain injuries to the joint surface, which can lead to premature arthritis, as articular cartilage does not heal. Thus, a method is needed for biological repair or regeneration of cartilage. The long-term objective of this work is to optimize cartilage repair by understanding how the cascade of events in neochondrogenesis (new cartilage formation) is regulated. For this to be achieved, a thorough understanding of the molecular mechanisms regulating cartilage formation and repair is required. Recent advances in tissue and the cell transplantation offer promise of hope for patients who could benefit from cartilage repair. The mechanisms by which undifferentiated mesenchymal cells (chondrocyte precursors) detect mechanical stimuli are unknown. Although chondrogenesis diminishes with age, it is clear that it is significantly enhanced through the use of mechanical stimuli, such as continuous passive motion. The investigators have developed a unique organ culture model using periosteal explants suspended in argarose in a mechanical environment. The unique feature of this model is that it mimics the in vivo repair of cartilage, from proliferation and differentiation of prechondrocytes, into chondrocytes and, thereafter, matrix synthesis. The goal of this grant proposal is to use this in vitro system to analyze the cellular responses of cartilage repair tissue to biomechanical stimuli using cyclical changes in hydrostatic pressure, which are referred to as dynamic fluid pressure (DFP). The project's Specific Aims are to (1) determine if cell proliferation is required for chondrogenesis; (2) characterize the phenotypic changes during DFP-mediated chondrogenesis; (3) identify mediators of DFP action during periosteal chondrogenesis; and (4) determine the age-related changes in the response of periosteum to DFP as a preliminary to understanding how and why the cartilage repair potential declines with age. It is suggested that the translational research proposed in this application is important because cartilage repair techniques, such as periosteal transplantation, are currently used to treat patients. Findings from these studies establish parameters for mechanical stimulation of tissue-engineered cartilage and a framework on which further research and tissue engineering of cartilage repair can be based, including how cells interact during paracrine regulation. It is felt that these findings will have relevance to other important area of orthopedics, including fracture healing, and have significant potential to impact the care of patients.