WNT Signaling and Bone: Lessons From Skeletal Dysplasias and Disorders
| Autor: | Eveline Boudin, Wim Van Hul, Yentl Huybrechts, Geert Mortier |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Frizzled Endocrinology Diabetes and Metabolism Osteoporosis Review lcsh:Diseases of the endocrine glands. Clinical endocrinology chemistry.chemical_compound 0302 clinical medicine Endocrinology BRACHYDACTYLY TYPE-B Receptor SCLEROSTIN skeletal dysplasias Wnt Signaling Pathway LRP5 MUTATIONS Wnt signaling pathway Phenotype Cell biology SOST GENE medicine.anatomical_structure CAUSES TETRA-AMELIA Signal transduction Bone Diseases MASS PHENOTYPE Life Sciences & Biomedicine Wingless and int-1 (WNT)/beta-catenin pathway 030209 endocrinology & metabolism Biology Bone and Bones 03 medical and health sciences Endocrinology & Metabolism MISSENSE MUTATION RECESSIVE ROBINOW-SYNDROME Wingless and int-1 (WNT)/Ca2+ pathway medicine Wingless and int-1 (WNT)/β-catenin pathway Animals Humans NONSENSE MUTATION Wingless and Int-1 (WNT)/planar cell polarity (PCP) pathway Science & Technology lcsh:RC648-665 Cartilage Genetic Diseases Inborn medicine.disease osteoporosis AUTOSOMAL-DOMINANT OMODYSPLASIA Musculoskeletal Abnormalities 030104 developmental biology chemistry Sclerostin Human medicine |
| Zdroj: | Frontiers in Endocrinology Frontiers in Endocrinology, Vol 11 (2020) Frontiers in endocrinology |
| ISSN: | 1664-2392 |
| Popis: | Skeletal dysplasias are a diverse group of heritable diseases affecting bone and cartilage growth. Throughout the years, the molecular defect underlying many of the diseases has been identified. These identifications led to novel insights in the mechanisms regulating bone and cartilage growth and homeostasis. One of the pathways that is clearly important during skeletal development and bone homeostasis is the Wingless and int-1 (WNT) signaling pathway. So far, three different WNT signaling pathways have been described, which are all activated by binding of the WNT ligands to the Frizzled (FZD) receptors. In this review, we discuss the skeletal disorders that are included in the latest nosology of skeletal disorders and that are caused by genetic defects involving the WNT signaling pathway. The number of skeletal disorders caused by defects in WNT signaling genes and the clinical phenotype associated with these disorders illustrate the importance of the WNT signaling pathway during skeletal development as well as later on in life to maintain bone mass. The knowledge gained through the identification of the genes underlying these monogenic conditions is used for the identification of novel therapeutic targets. For example, the genes underlying disorders with altered bone mass are all involved in the canonical WNT signaling pathway. Consequently, targeting this pathway is one of the major strategies to increase bone mass in patients with osteoporosis. In addition to increasing the insights in the pathways regulating skeletal development and bone homeostasis, knowledge of rare skeletal dysplasias can also be used to predict possible adverse effects of these novel drug targets. Therefore, this review gives an overview of the skeletal and extra-skeletal phenotype of the different skeletal disorders linked to the WNT signaling pathway. ispartof: FRONTIERS IN ENDOCRINOLOGY vol:11 ispartof: location:Switzerland status: published |
| Databáze: | OpenAIRE |
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