Boning up on glypicans - opportunities for new insights into bone biology

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dc.contributor.authorDwivedi, P.
dc.contributor.authorLam, N.
dc.contributor.authorPowell, B.
dc.date.issued2013
dc.description.abstractBone formation is remarkable for the convergence in the activity of four major signalling pathways, the bone morphogenetic protein (BMP), fibroblast growth factor (FGF), hedgehog (HH) and wingless-integrated (WNT) pathways. These pathways cooperate in morphogenetic, proliferative and differentiative processes that underpin the development, growth and repair of skeletal structures. They are regulated by pathway-specific modulators and by another class of molecules, the glypicans. Glypicans are proteoglycans located on the cell surface, where they act as coreceptors to promote or inhibit signalling by ligands of the BMP, FGF, HH and WNT pathways, through protein-protein and protein-carbohydrate interactions. In this review, we discuss glypican structure, expression and function in the context of bone development and growth, with emphasis on the long bone growth plate where five of the six glypicans are expressed in overlapping patterns in the chondrogenic zone. Analyses of gene knockout models and the human conditions of Simpson-Golabi-Behmel syndrome and omodysplasia, which arise from mutations in glypican 3 (GPC3) and GPC6, respectively, highlight both subtle and striking effects of glypicans on bone growth. We draw attention to challenges and areas of opportunity, where the actions of glypicans on BMP, FGF, HH and WNT signalling might be profitably studied to help illuminate the complex interplay of signalling that drives bone growth.
dc.description.statementofresponsibilityP. P. Dwivedi, N. Lam and B. C. Powell
dc.identifier.citationCell Biochemistry and Function, 2013; 31(2):91-114
dc.identifier.doi10.1002/cbf.2939
dc.identifier.issn0263-6484
dc.identifier.issn1099-0844
dc.identifier.urihttp://hdl.handle.net/2440/79232
dc.language.isoen
dc.publisherJohn Wiley & Sons Ltd
dc.rightsCopyright © 2013 John Wiley & Sons, Ltd.
dc.source.urihttps://doi.org/10.1002/cbf.2939
dc.subjectglypican
dc.subjectbone
dc.subjectendochondral
dc.subjectchondrocyte
dc.subjectreceptor
dc.subjectBMP
dc.subjectWNT
dc.subjecthedgehog
dc.titleBoning up on glypicans - opportunities for new insights into bone biology
dc.typeJournal article
pubs.publication-statusPublished

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