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• W2019663306 abstract "There are many crucial genes and signaling pathways in the proper development of an organism. Pathologies may arise from a deregulation of these pathways. The Indian Hedgehog–PTH-related protein (Ihh-PTHrP) pathway is vital in the proper development of endochondral bones, such as the long bones. The Ihh-PTHrP pathway regulates the rate at which chondrocytes within the growth plate proliferate and differentiate. Thus, this pathway allows for the longitudinal growth of bones. However, a disruption in this pathway may lead to enchondromas and osteochondromas, which are both childhood cartilaginous neoplasms. Recently, our lab identified a mutant receptor for PTHrP in enchondroma samples. Mice expressing this mutant receptor and mice with increased Ihh activity develop conditions similar to human enchondromatosis. Linkage analysis shows an association between EXT genes and osteochondromas in hereditary multiple exostoses syndrome. Studies in Drosophila and mice suggest EXT gene products play a role in the diffusion of hedgehog proteins. A mutation in EXT genes may result in an abnormal Ihh diffusion pattern leading to an osteochondroma. There are agents that inhibit Hedgehog signaling. These agents may be useful in the treatment of enchondromas and osteochondromas. This review will discuss the discovery of the Ihh-PTHrP pathway and its involvement in neoplasia, and will suggest possible novel therapeutic agents in the treatment of these cartilaginous neoplasms." @default.
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• W2019663306 date "2003-04-01" @default.
• W2019663306 modified "2023-10-15" @default.
• W2019663306 title "Developmental Pathways in Musculoskeletal Neoplasia: Involvement of the Indian Hedgehog-Parathyroid Hormone-Related Protein Pathway" @default.
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• W2019663306 doi "https://doi.org/10.1203/01.pdr.0000054688.93486.18" @default.
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