MECHANICAL FACTORS IN CARTILAGE REPAIR

描述(改编自申请者摘要)：每年，数千名 年轻人关节表面受伤，可能导致早产 关节炎，因为关节软骨不能愈合。因此，需要一种方法来 软骨的生物修复或再生。这样做的长期目标是 我们的工作是通过了解一系列事件如何影响软骨修复 在新软骨生成(新的软骨形成)中是受调控的。要做到这一点 实现了对分子调控机制的透彻理解 软骨的形成和修复是必需的。组织和血管内皮细胞的最新进展 细胞移植为患者带来了希望，他们可以受益于 软骨修复。未分化间充质细胞的机制 (软骨细胞前体)检测机械刺激是未知的。虽然 软骨生成随着年龄的增长而减少，显然它是显著的 通过使用机械刺激来增强的，如持续被动 动议。研究人员开发了一种独特的器官培养模型，使用 在机械环境中，骨膜外植体悬浮在琼脂中。这个 这个模型的独特之处在于它模仿了软骨的体内修复， 从前软骨细胞的增殖和分化，到软骨细胞 然后，进行矩阵合成。这项拨款提案的目标是使用 该体外系统用于分析软骨修复的细胞反应 使用流体静压的周期性变化对组织进行生物力学刺激， 它们被称为动态流体压力(DFP)。该项目的具体内容 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) 确定DFP在骨膜软骨形成过程中的作用介体；以及(4) 确定骨膜对DFP反应的年龄相关变化 初步了解软骨修复的方式和原因 随着年龄的增长而下降。有人建议，#年提出的翻译研究 这一应用非常重要，因为软骨修复技术，如 骨膜移植，目前都用于治疗患者。调查结果来自 这些研究建立了机械刺激的参数 组织工程化软骨及其进一步研究和应用的框架 软骨修复的组织工程学基础，包括细胞如何 旁分泌调节过程中的相互作用。人们认为，这些发现将具有 与骨科的其他重要领域相关，包括骨折愈合， 并且有很大的潜力影响病人的护理。

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.