AGE DEPENDENT REGULATION OF PERIOSTEAL CHONDROGENESIS

描述(改编自申请人的摘要)：广泛的实验室 首席调查员的手术经验证明 损伤关节的软骨再生和生物表面处理 有可能使用骨膜移植。但是，主要的限制是 骨膜生成软骨的能力随年龄增长而降低 在成年早期以后的受试者中。下一步是记录 骨膜软骨形成过程中细胞事件的增龄性变化 调节患者的因素。骨膜外植体培养模型的建立 由首席调查员提供，现在可以在 体外实验，为实现这一目标而进行的一系列逻辑假设。在……里面 具体目标1，将确定是否年龄相关的下降 骨膜的软骨形成潜能与骨膜的变化相关 软骨细胞前体细胞频率、增殖和/或分化。 具体目标2将重点放在对增殖的调控上，测试 生长激素和胰岛素样生长因子(IGF-1)假说 调节骨膜内软骨细胞前体细胞的增殖。下一首, 具体目标3将测试我们模型的有效性，即核扩散和 分化是依赖于序列的，允许更准确地计时 研究或控制这两种事件中的任何一种。最后，在具体目标4中， 这将被确定是否年龄相关的软骨形成潜力 骨膜与某些生长因子(或 他们的受体)，已知的调节软骨细胞，IGF-1和转化生长因子-β，将 要下定决心。社会的影响和教育质量的提高 数以千计的患者遭受或面临着 如果能在#年预防关节炎，发展中的关节炎将是深远的。 许多人，并在另一些人中接受治疗，通过生物表面处理。

DESCRIPTION (Adapted from the applicant's Abstract): Extensive laboratory and surgical experience by the Principal Investigator has proven that cartilage regeneration and biological resurfacing of damaged joints is possible using periosteal grafts. However, the major limitation is an age-dependent decrease in the potential of periosteum to produce cartilage in subjects beyond early adulthood. The next step is to document age-related changes in the cellular events in periosteal chondrogenesis and factors regulating patients. The periosteal explant culture model developed by the Principal Investigator makes it now possible to pose and test, in vitro, a logical series of hypotheses to achieve this objective. In Specific Aim 1, it will be determined if the age-dependent decrease in chondrogenic potential of the periosteum correlates with changes in chondrocyte precursor cell frequency, proliferation and/or differentiation. Specific Aim 2 will focus on regulation of proliferation, testing the hypothesis that growth hormone (GH) and insulin-like growth factor (IGF-1) regulate proliferation of chondrocyte precursors in the periosteum. Next, Specific Aim 3 will test the validity of our model, that proliferation and differentiation are sequence-dependent, permitting more accurate timing of the study or control of either of these events. Finally, in Specific Aim 4, it will be determined if the age-dependent chondrogenic potential of the periosteum is related to altered activity of certain growth factors (or their receptors) known to regulate chrondrocytes, IGF-1 and TGF-beta, will be determined. The impact of society and the improvement in the quality of life for so many thousands of patients suffering from, or at risk of developing, arthritis would be profound if arthritis could be prevented in many, and treated in others, with biological resurfacing.