AGE DEPENDENT REGULATION OF PERIOSTEAL CHONDROGENESIS

描述（改编自申请人摘要）：大型实验室 主要研究者的手术经验证明， 受损关节的软骨再生和生物表面重建是 可能会用到骨膜移植 然而，主要的限制是 年龄依赖性降低骨膜产生软骨的潜力 在成年早期以后的研究对象中。 下一步是记录 年龄相关的变化，在骨膜软骨发生的细胞事件， 调节患者的因素。 建立了骨膜植块培养模型 由首席研究员现在可以摆姿势和测试， 体外，一系列合乎逻辑的假设，以实现这一目标。 在 具体目标1，将确定是否年龄依赖性降低 骨膜的软骨形成潜力与 软骨细胞前体细胞频率、增殖和/或分化。 具体目标2将侧重于增殖的调节， 生长激素和胰岛素样生长因子假说 调节骨膜中软骨细胞前体的增殖。 接下来， 具体目标3将测试我们的模型的有效性，即增殖和 分化是序列依赖性的，允许更准确的定时， 对这些事件的研究或控制。 在第四个具体目标中， 将确定是否年龄依赖性软骨形成的潜力， 骨膜与某些生长因子（或 它们的受体）已知调节软骨细胞，IGF-1和TGF-β， 被确定。 社会的影响和质量的提高 成千上万的患者患有或面临 发展中国家，关节炎将是深刻的，如果关节炎可以预防， 许多人，并在其他治疗，与生物表面。

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.