CROSSTALK BETWEEN HEDGEHOG AND IGF SIGNALING IN OSTEOPROGENITORS

摘要 对成体骨祖细胞及其成骨细胞调控分子机制的基本认识 分化是开发新的骨合成代谢疗法的关键。我们最近做了 发现HH信号诱导IGF信号成分的表达并激活IGF 因此，在成骨细胞系细胞中参与了HH-IGF阳性摄食循环。此外，我们 已经确定HH反应人群是成人骨骼中关键的骨祖细胞。在当前 建议，我们将进一步阐明HH-IGF反馈机制的生化基础，以及 探讨生后成骨细胞和成骨细胞调控环的生理学相关性 骨形成。总体而言，该项目的成功完成将提供新的机械洞察力 关于成人骨骼中的HH-IGF信号转导，并可能为开发有效的骨骼开辟新的途径 合成代谢疗法。

Abstract A fundamental understanding of the molecular mechanism governing adult osteoprogenitors and their differentiation is essential for developing novel bone anabolic therapeutics. We have recently discovered that Hh signaling induces expression of Igf signaling components and activates Igf signaling, thus engaging in a Hh-Igf positive feedabck loop in osteoblast-lineage cells. In addition, we have identified a Hh-responsive population as critical osteoprogenitors in adult bones. In the current proposal, we will further elucidate the biochemical basis for the Hh-Igf feedback mechanism, and explore the physiological relevance of the regulatory loop in postnatal osteoprogenitors and adult bone formation. Overall, successful completion of this project will provide novel mechanistic insights about Hh-Igf signaling in adult bones, and may open new avenues for developing effective bone anabolic therapeutics.