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dc.contributor.authorLing, Ling
dc.contributor.authorMurali, Sadasivam
dc.contributor.authorDombrowski, Christian
dc.contributor.authorM. Haupt, Larisa
dc.contributor.authorS. Stein, Gary
dc.contributor.authorJ. Van Wijnen, Andre
dc.contributor.authorNurcombe, Victor
dc.contributor.authorM. Cool, Simon
dc.date.accessioned2017-05-03T16:58:44Z
dc.date.available2017-05-03T16:58:44Z
dc.date.issued2006
dc.date.modified2009-12-07T03:38:53Z
dc.identifier.issn00219541
dc.identifier.doi10.1002/jcp.20760
dc.identifier.urihttp://hdl.handle.net/10072/27151
dc.description.abstractFibroblast growth factor-2 (FGF2) is a powerful promoter of bone growth. We demonstrate here that brief exposure to FGF2 enhances mineralized nodule formation in cultured rat osteoprogenitor cells due to an expansion of cells that subsequently mineralize. This mitogenic effect is mediated via sulfated glycosaminoglycans (GAGs), FGFR1, and the extracellular signal-regulated kinase (ERK) pathway. The GAGs involved in this stimulation are chondroitin sulfates (CS) rather than heparan sulfates (HS). However, continuous FGF2 treatment reduces alkaline phosphatase (ALP) activity, downregulates collagen I1 (ColI1) and FGFR3 expression, upregulates the expression and secretion of osteopontin (OPN) and inhibits mineralization. The inhibitory effects of FGF2 on FGFR3 expression and ALP activity are also mediated by the ERK pathway, although the effects of FGF2 on ColI1 and OPN expression are mediated by GAGs and PKC activity. Thus short-term activation of FGF2/FGFR1 promotes osteoprogenitor proliferation and subsequent differentiation, while long-term activation of FGF2 signaling disrupts mineralization by modulating osteogenic marker expression. This study thus establishes the central role of sulfated GAGs in the osteogenic progression of osteoprogenitors.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherJohn Wiley & Sons, Inc.
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom811
dc.relation.ispartofpageto825
dc.relation.ispartofissue3
dc.relation.ispartofjournalJournal of Cellular Physiology
dc.relation.ispartofvolume209
dc.rights.retentionY
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchMedical Physiology
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode1116
dc.titleSulfated glycosaminoglycans mediate the effects of FGF2 on the osteogenic potential of rat calvarial osteoprogenitor cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2006
gro.hasfulltextNo Full Text
gro.griffith.authorHaupt, Larisa


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