FGFR3 Deficiency Causes Multiple Chondroma-like Lesions by Upregulating Hedgehog Signaling

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Benign cartilaginous tumors, especially osteochondromas and enchondromas, are the most common primary bone tumors in humans. Several hereditary diseases are characterized by the development of cartilaginous tumors, including hereditary multiple exostoses, metachondromatosis, and enchondromatosis, which are caused by mutations in genes such as exostosin 1 and 2, tyrosine protein phosphatase non-receptor type 11, parathyroid hormone receptor 1, and isocitrate dehydrogenase 1 and 2. The proteins encoded by these genes are directly or indirectly linked to fibroblast growth factor (FGF) signaling. In addition, osteochondroma was found in several members of a family with camptodactyly, tall stature, and hearing loss syndrome, a rare inherited disorder caused by a heterozygous missense mutation in Fgfr3. In this study, we found that Fgfr3 deficiency leads to the formation of cartilaginous tumors, including osteochondromas and enchondromas, likely due to dysregulated endochondral ossification in growth plates. We also show that cartilaginous tumorigenesis in Fgfr3-deficient mice results from excessive Indian hedgehog production mediated by the activation of mitogen-associated protein kinase signaling. Based on these results, we propose a model for cartilaginous tumor development in which FGFR3 functions as a tumor suppressor. Our findings also suggest that modulation of FGFR3 and related signaling pathways is a potential therapeutic strategy for treating benign cartilaginous tumors.

Vyšlo v časopise: FGFR3 Deficiency Causes Multiple Chondroma-like Lesions by Upregulating Hedgehog Signaling. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005214
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005214

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