IN VITRO CHONDROGENESIS OF BONE MARROW MESENCHYMAL CELLS

描述（申请人的逐字记录）：我们开发并表征了 一种体外培养系统，其促进软骨细胞的成软骨分化， 哺乳动物间充质祖细胞。我们现在建议使用该系统， 探索软骨形成的阶段，包括从冷凝到 软骨细胞外基质分子的表达。最近的证据 提示MAP激酶通路在控制进展中的作用。 此外，p38 MAPK的作用类似于用 软骨形成过程中的Wnt/β-连环蛋白信号传导。Wnt通路可能与 MAP激酶，这些联合收割机调节进展。Wnts是一个家庭 在发育过程中起重要作用的分泌蛋白质。Wnt 已经暗示参与软骨形成，但不清楚哪些Wnt 重要. Wnt结合蛋白Frzbs对Wnt作用的调节可能是 另一个控制软骨形成进展的水平。总体假设 是一个具体的，协调的和时间的调节冷凝相关的， 蛋白质是从缩合到基质生产的过程所必需的 在软骨形成过程中。检验这一假设的具体目的是：（1） 表征进展过程中ERK 1/2和p38 MAPK信号传导;（2） 表征在进展过程中起作用的Wnt途径;以及（3） 确定Frzb的作用，Frzb是Wnt结合蛋白， 软骨形成这项工作将进一步加深我们对软骨形成的理解。 从祖细胞分化。这可能有利于设计新的 软骨相关问题的治疗策略。

DESCRIPTION (Verbatim from the Applicant): We have developed and characterized an in vitro culture system that facilitates the chondrogenic differentiation of mammalian mesenchymal progenitor cells. We now propose to use the system to explore the stage of chondrogenesis involving progression from condensation to expression of cartilage extracellular matrix molecules. Recent evidence suggests a role for the MAP kinase pathways in controlling progression. Furthermore, the effects of p38 MAPK are similar to those seen with Wnt/beta-catenin signaling during chondrogenesis. Wnt pathways may be linked to the MAP kinases, and these combine to regulate progression. Wnts are a family of secreted proteins that appear to have important roles in development. Wnt involvement in chondrogenesis has been implied but it is unclear which Wnts are important. Modulation of Wnt action by Frzbs, the Wnt binding proteins, may be another level of control for chondrogenic progression. The overall hypothesis is that a specific, coordinated and temporal regulation of condensation-related proteins is necessary for progression from condensation to matrix production during chondrogenesis. The Specific Aims to test this hypothesis are: (1) to characterize ERK 1/2 and p38 MAPK signaling during progression; (2) to characterize the Wnt pathways that operate during progression; and (3) to determine the role of Frzb, the Wnt binding protein expressed during chondrogenesis. This work will further our understanding of chondrogenic differentiation from progenitor cells. This may be of benefit for designing new therapeutic strategies for cartilage-related problems.