Coordinated fibroblast growth factor and heparan sulfate regulation of osteogenesis

Jackson, Rebecca; Nurcombe, Victor; Cool, Simon M.

doi:10.1016/j.gene.2006.04.028

Cited by 72 publications

(64 citation statements)

References 148 publications

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“…Molecular evidence has shown that a large proportion of FGF signals are transduced through activation of the MAPK pathways, by which the binding of FGF to FGF receptors causes FGFR dimerization and subsequent autophosphorylation of intrinsic tyrosine residues. This, in turn, leads to the downstream activation of distinct MAPK pathways (Jackson et al, 2006). Previous studies have shown that RA mediates MAPK pathways in mediating both normal and malignant cell differentiation (Hoffman et al, 2003;Wang, 2005).…”

Section: Ra-mediated Rara Hypophosphorylation Induces Fgf8f Expressionmentioning

confidence: 99%

“…Although many studies have shown that FGF8 regulates osteoblast development and bone formation (Ornitz and Marie, 2002;Jackson et al, 2006), the distinct physiological functions of different FGF8 isoforms in such regulations are unknown. We find that both RA and RARaS77A induce FGF8f expression in U2OS cells (Figure 6f; Supplementary Figure 2A, 7B-E and 8C-E).…”

Section: Ra-mediated Rara Hypophosphorylation Induces Fgf8f Expressionmentioning

confidence: 99%

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Retinoid-suppressed phosphorylation of RARα mediates the differentiation pathway of osteosarcoma cells

et al. 2010

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Section: Ra-mediated Rara Hypophosphorylation Induces Fgf8f Expressionmentioning

confidence: 99%

Section: Ra-mediated Rara Hypophosphorylation Induces Fgf8f Expressionmentioning

confidence: 99%

Retinoid-suppressed phosphorylation of RARα mediates the differentiation pathway of osteosarcoma cells

et al. 2010

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“…(24,25) Thus, although the expression of the klotho gene has not been detected in bones even by RT-PCR, (26) its secreted form is present in the systemic circulation. (26,27) Given that FGF23 is most highly expressed in bones (10)(11)(12) and that multiple FGFs and FGFRs have been implicated in skeletal development, (20,21) we therefore hypothesize that FGF23 has a direct role in bone formation. To test this, we analyzed the effects of overexpression of human FGF23 (hFGF23) on bone formation in the well-established fetal rat calvaria (RC) cell and organ culture models.…”

mentioning

confidence: 99%

Overexpression of Fibroblast Growth Factor 23 Suppresses Osteoblast Differentiation and Matrix Mineralization In Vitro

Wang

Yoshiko

Yamamoto

et al. 2008

Journal of Bone and Mineral Research

242

183

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ABSTRACT:Introduction: Fibroblast growth factor (FGF)23 is produced primarily in bone and acts on kidney as a systemic phosphaturic factor; high levels result in rickets and osteomalacia. However, it remains unclear whether FGF23 acts locally and directly on bone formation. Materials and Methods: We overexpressed human FGF23 in a stage-specific manner during osteoblast development in fetal rat calvaria (RC) cell cultures by using the adenoviral overexpression system and analyzed its effects on osteoprogenitor proliferation, osteoid nodule formation, and mineralization. Bone formation was also measured by calcein labeling in parietal bone organ cultures. Finally, we addressed the role of tyrosine phosphorylation of FGF receptor (FGFR) in mineralized nodule formation. Results: Nodule formation and mineralization, but not osteoprogenitor proliferation, were independently suppressed by overexpression of FGF23 in RC cells. Increased FGF23 levels also suppressed bone formation in the parietal bone organ culture model. FGF23 overexpression enhanced phosphorylation of FGFR, whereas the impairment of mineralized nodule formation by FGF23 overexpression was abrogated by SU5402, an inhibitor of FGFR1 tyrosine kinase activity. Conclusions: These studies suggest that FGF23 overexpression suppresses not only osteoblast differentiation but also matrix mineralization independently of its systemic effects on Pi homeostasis.

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“…Heparin/heparan sulfate binds to growth factors, including BMP, the fibroblast growth factor (FGF) family, heparin-binding epidermal growth factor, and vascular endothelial growth factor [19,[29][30][31], as well as to extracellular matrix molecules such as fibronectin, vitronectin, and laminin [20]. Proteoglycans have been identified within bone extracellular matrices and are known to play a role in mineralization and bone formation.…”

Section: Discussionmentioning

confidence: 99%

Amelogenin binds to both heparan sulfate and bone morphogenetic protein 2 and pharmacologically suppresses the effect of noggin

Saito

Konishi

Nishiguchi

et al. 2008

Bone

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Enamel matrix derivative (EMD) is widely considered useful to promote tissue regeneration during periodontal treatment. It has been reported that the main constituent of EMD is amelogenin and that the BMP-like and TGF-β-like activity of EMD promotes osteogenesis. However, it remains unclear whether those activities are dependent on amelogenin or another growth factor contained in EMD. We performed two-dimensional SDS-PAGE analysis of EMD, as well as Western blot analyses using anti-amelogenin, anti-BMP2/4, and anti-TGF-β1 antibodies, and amino acid sequencing. Our results revealed that a large number of splicing forms of amelogenin, BMP2/4, and other unknown molecules were involved in EMD, though TGF-β1 was not. In addition, we have evaluated intracellular signaling of ERK1/2 and Smad1/5/8, binding potential and alkaline phosphatase activity and have explored the potential regulatory relationship between amelogenin and BMP. Amelogenin bound to BMP2 as well as heparin/heparan sulfate. Thus, it was suggested that BMP2/4 carried over in EMD during processing promote binding activity and phosphorylate Smad1/5/8 in osteoblasts. On the other hand, amelogenin did not phosphorylate Smad1/5/8, but rather 3 ERK1/2. Further, high density amelogenin reduced the inhibition of alkaline phosphatase activity by noggin, though amelogenin did not have antagonistic properties against BMP. Together with the above findings, our findings suggest that the BMP2/4 contaminated during the purification process of EMD because of the avidity of amelogenin plays an important role in signaling pathway of calcification.4

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Coordinated fibroblast growth factor and heparan sulfate regulation of osteogenesis

Cited by 72 publications

References 148 publications

Retinoid-suppressed phosphorylation of RARα mediates the differentiation pathway of osteosarcoma cells

Retinoid-suppressed phosphorylation of RARα mediates the differentiation pathway of osteosarcoma cells

Overexpression of Fibroblast Growth Factor 23 Suppresses Osteoblast Differentiation and Matrix Mineralization In Vitro

Amelogenin binds to both heparan sulfate and bone morphogenetic protein 2 and pharmacologically suppresses the effect of noggin

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