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dc.contributor.authorLing, Ling
dc.contributor.authorMurali, Sadasivam
dc.contributor.authorDombrowski, Christian
dc.contributor.authorHaupt, Larisa M.
dc.contributor.authorStein, Gary S.
dc.contributor.authorVan Wijnen, Andre J.
dc.contributor.authorNurcombe, Victor
dc.contributor.authorCool, Simon M.
dc.date2022-08-11T08:09:01.000
dc.date.accessioned2022-08-23T16:15:30Z
dc.date.available2022-08-23T16:15:30Z
dc.date.issued2006-09-15
dc.date.submitted2008-11-05
dc.identifier.citationJ Cell Physiol. 2006 Dec;209(3):811-25. <a href="http://dx.doi.org/10.1002/jcp.20760 ">Link to article on publisher's site</a>
dc.identifier.issn0021-9541 (Print)
dc.identifier.doi10.1002/jcp.20760
dc.identifier.pmid16972247
dc.identifier.urihttp://hdl.handle.net/20.500.14038/34104
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 Ialpha1 (ColIalpha1) 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 ColIalpha1 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.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16972247&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1002/jcp.20760
dc.subjectAlkaline Phosphatase; Animals; Calcification, Physiologic; Cell Proliferation; Cells, Cultured; Collagen Type I; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; inhibitors; Fibroblast Growth Factor 2; *Glycosaminoglycans; Humans; Osteogenesis; Osteopontin; Rats; Rats, Wistar; Receptor, Fibroblast Growth Factor, Type 1; Skull; Stem Cells; Sulfates
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleSulfated glycosaminoglycans mediate the effects of FGF2 on the osteogenic potential of rat calvarial osteoprogenitor cells
dc.typeJournal Article
dc.source.journaltitleJournal of cellular physiology
dc.source.volume209
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/768
dc.identifier.contextkey661877
html.description.abstract<p>Fibroblast 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 Ialpha1 (ColIalpha1) 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 ColIalpha1 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.</p>
dc.identifier.submissionpathgsbs_sp/768
dc.contributor.departmentDepartment of Cell Biology
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages811-25


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