CROSSTALK BETWEEN HEDGEHOG AND IGF SIGNALING IN OSTEOPROGENITORS

摘要 对成人骨祖细胞及其分化的分子机制的基本认识 分化对于开发新的骨合成代谢治疗剂是必需的。我们最近 发现Hh信号诱导Igf信号成分的表达并激活Igf 信号传导，从而参与成骨细胞系细胞中的Hh-Igf阳性反馈循环。另外我们 已经确定了一个Hh-反应人群作为成人骨骼中的关键骨祖细胞。在当前 建议，我们将进一步阐明Hh-Igf反馈机制的生化基础， 探讨出生后骨祖细胞和成年后骨祖细胞调节环的生理相关性 骨形成总的来说，这个项目的成功完成将提供新的机制见解 关于成人骨骼中的Hh-Igf信号传导，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.