BMPS IN SKELETAL GROWTH AND OSTEOGENIC DIFFERENTIATION

描述：骨形态发生蛋白(BMPs)是骨形态发生蛋白的重要调节因子。 成骨作用。至少9种不同的BMP诱导异位骨形成，以及 这些蛋白质大多在骨骼组织中表达。BMP3，一种发散型 骨形态发生蛋白家族的成员，是成人骨骼中含量最丰富的骨形态发生蛋白之一， 然而，人们对它作为成骨调节因子的功能知之甚少。 承诺/差异化。最近，与BMP3b密切相关的基因BMP3b BMP3，已被描述。骨形态发生蛋白多个成员的表达 骨子里的家庭表明，BMP要么具有重叠的功能，要么 单个BMP在软骨和骨骼中发挥着不同的作用。的目标是 本研究旨在探讨BMP3和BMP3b在成骨过程中的作用。 承诺/差异化。非洲爪哇测试的初步结果显示 与成骨BMPs相比，BMP3具有独特的作用。 初步的体外数据显示，BMP3和BMP3b具有阳性或 对成骨分化的负面影响，取决于 表情。因此，我们的[申请者的]结果表明，BMP3和 BMP3b可能对成骨分化有拮抗作用， 提示BMP3和BMP3b在体内的作用可能是调节 骨形成的水平。为了验证这一假设，BMP3突变体 老鼠已经诞生了。BMP 3-/-小鼠将在形态上进行分析， 组织学、放射学和生物力学水平。初步结果 提示BMP3在体内负向调节骨密度。为了测试 BMP3和BMP3b在成骨过程中是否具有重叠功能， 我们将分析BMP3和3b的表达模式。对基因进行测试 BMP3b是否在体内影响骨生理，BMP3b-/-小鼠将 已生成。测试BMP3和3b在 骨骼组织，BMP3/BMP3b复合突变体将被检测。这个 BMP3和BMP3b修改其他BMP效果的能力将是 检查过了。因为初步数据表明BMP3和BMP3b，即 在成人骨骼中含量丰富，可能对 体外、体内功能测试，如靶标菌株的分析 对于理解这些生长因子所起的作用是必不可少的 在成人的骨头里。据建议，这些信息将有助于我们的 全面了解BMPs在成骨前体细胞中的作用 并可能建议潜在的治疗方法，如关节炎和 骨质疏松症，以BMP3活性增强或抑制为基础。

DESCRIPTION: Bone Morphogenetic Proteins (BMPs) are essential regulators of osteogenesis. At least 9 different BMPs induce ectopic bone formation, and most of these proteins are expressed in skeletal tissues. BMP3, a divergent member of the BMP family, is one of the most abundant BMPs in adult bone, yet little is known about its function as a regulator of osteogenic commitment/ differentiation. Recently, BMP3b, a gene closely related to BMP3, has been described. The expression of multiple members of the BMP family in bone suggests that either BMPs serve overlapping functions, or that individual BMPs play distinct roles in cartilage and bone. The goal of this proposal is to investigate the roles of BMP3 and BMP3b in osteogenic commitment/ differentiation. Preliminary results from Xenopus assays show that BMP3 has unique effects compared to those of osteogenic BMPs. Preliminary in vitro data show that BMP3 and BMP3b have either positive or negative effects on osteogenic differentiation, depending on the context of expression. Therefore, our [the applicants'] results indicate that BMP3 and BMP3b may have antagonistic effects on osteogenic differentiation, suggesting that the roles of BMP3 and BMP3b in vivo may be to modulate levels of bone formation. In order to test this hypothesis, BMP3 mutant mice have been generated. BMP 3-/-mice will be analyzed on a morphological, histological, radiological and biomechanical level. Preliminary results suggest that BMP3 negatively regulates bone density in vivo. To test whether BMP3 and BMP3b may have overlapping functions in osteogenesis, expression patterns for BMP3 and 3b will be analyzed. To test genetically whether BMP3b affects bone physiology in vivo, BMP3b-/- mice will be generated. To test whether BMP3 and 3b have overlapping functions in skeletal tissues, compound BMP3/BMP3b mutants will be examined. The abilities of BMP3 and BMP3b to modify the effects of other BMPs will be examined. Because the preliminary data indicate that BMP3 and BMP3b, which are abundant in adult bone, may have either positive or negative effects in vitro, in vivo tests of function, such as the analysis of targeted strains of mice, are essential to understanding the role these growth factors play in adult bone. It is suggested that this information will contribute to our overall understanding of the roles of BMPs in osteogenic precursor cells, and may suggest potential therapies for conditions, such as arthritis and osteoporosis, based on augmentation or inhibition of BMP3 activity.