Crosstalk between Hedgehog and IGF Signaling in Osteoprogenitors

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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.