Fibroblast Growth Factor 2 Induction of the Osteocalcin Gene Requires MAPK Activity and Phosphorylation of the Osteoblast Transcription Factor, Cbfa1/Runx2

Xiao, Guozhi; Jiang, Di; Gopalakrishnan, Rajaram; Franceschi, Renny T.

doi:10.1074/jbc.m206057200

Cited by 358 publications

(327 citation statements)

References 49 publications

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“…As noted above the expression of Runx2 can be stimulated by factors such as BMPs or inhibited by PTHrP. Runx2 phosphorylation can also regulate its transcriptional activity [Xiao et al, 2002] and additional factors also interact with Runx2 to regulate its transcriptional activity [Vega et al, 2004]. It is tempting to speculate that Runx2 may serve as a convergent point of multiple pathways orchestrating the transcription of Ihh, however, we have yet to determine if any of the factors regulating Runx2 play a role in regulation of Ihh in the growth plate.…”

Section: Prospectsmentioning

confidence: 92%

Indian hedgehog: Its roles and regulation in endochondral bone development

Lai

Mitchell

2005

J of Cellular Biochemistry

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Normal endochondral bone development requires the coordination of chondrocyte proliferation and differentiation. Indian hedgehog (Ihh) is a morphogen produced by chondrocytes in the early stage of terminal differentiation and plays several key roles in this process. Ihh regulates growth of adjacent proliferative chondrocytes and can also regulate the rate of differentiation of chondrocytes indirectly through its stimulation of parathyroid hormonerelated protein (PTHrP). In this review, we focus on recent studies that have identified new functions of Ihh and how Ihh itself is being regulated.

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Section: Prospectsmentioning

confidence: 92%

Indian hedgehog: Its roles and regulation in endochondral bone development

Lai

Mitchell

2005

J of Cellular Biochemistry

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“…[31] ERK can stimulate the osteoblast-related gene expression by extracellular matrix-integrin receptor interaction, BMP-2, growth factors, and mechanostressing. [31][32][33][34] Xiao et al [35] demonstrated that stimulation of MAPK enhances the expression of osteocalcin, whereas the ERK-specific inhibitor (PD98059) inhibits expression. Our data show that PD98059 significantly inhibits AOPP-induced calcium deposition and OPN expression, indicating that AOPP can promote osteoblast differentiation and calcification of HASMCs via the ERK pathway.…”

Section: Discussionmentioning

confidence: 99%

Advanced Oxidation Protein Products Induce Vascular Calcification by Promoting Osteoblastic Trans-Differentiation of Smooth Muscle Cells via Oxidative Stress and ERK Pathway

et al. 2009

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Vascular calcification is an actively regulated process similar to bone formation. Advanced oxidation protein products (AOPPs) have been demonstrated to be novel markers of oxidantmediated protein damage. The present study investigated the role of AOPPs in inducing osteoblastic trans-differentiation and calcification of smooth muscle cells in vitro. We found that AOPPs directly increased the calcium deposition and expression of core binding factor-a1 (CBF-a1) and osteopontin (OPN) and significantly decreased SM-a-actin expression in human aortic smooth muscle cells (HASMCs). AOPPs increased intracellular oxidative stress, which was inhibited by vitamin E. Vitamin E also inhibited AOPP-induced calcium content and osteoblast differentiation of HASMCs. Furthermore, the inhibitor of ERK significantly suppressed the effects of AOPPs on calcification and osteoblast marker expression. These findings suggest that AOPPs induce vascular calcification by promoting osteoblast differentiation of smooth muscle cells via oxidative stress and ERK pathway.

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“…Runt-related transcription factor-2 transcriptional activity is regulated by multiple pathways, such as the MAPK, PI3K, and STAT pathways (Lee et al, 2002;Xiao et al, 2002;Fujita et al, 2004). Runt-related transcription factor-2 also regulates several downstream target genes, such as extracellular matrix proteins, growth factors and receptors, mitochondrial proteins, and transcription factors (Gaikwad et al, 2001).…”

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confidence: 99%

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

et al. 2007

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Recent evidence suggests that Runt-related transcription factors play a role in different human tumours. In the present study, the localisation of the Runt-related transcription factor-2 (Runx2), its transcriptional activity, as well as its regulation of expression was analysed in human pancreatic ductal adenocarcinoma (PDAC). Quantitative real-time PCR and immunohistochemistry were used for Runx2 expression and localisation analysis. Runt-related transcription factor-2 expression was silenced using specific siRNA oligonucleotides in pancreatic cancer cells (Panc-1) and immortalised pancreatic stellate cells (IPSCs). Overexpression of Runx2 was achieved using a full-length expression vector. TGF-b1, BMP2, and other cytokines were assessed for their potential to regulate Runx2 expression. There was a 6.1-fold increase in median Runx2 mRNA levels in PDAC tissues compared to normal pancreatic tissues (Po0.0001). Runt-related transcription factor-2 was localised in pancreatic cancer cells, tubular complexes, and PanIN lesions of PDAC tissues as well as in tumour-associated fibroblasts/stellate cells. Coculture of IPSCs and Panc-1 cells, as well as treatment with TGF-b1 and BMP2, led to increased Runx2 expression in Panc-1 cells. Runt-related transcription factor-2 overexpression was associated with decreased MMP1 release as well as decreased growth and invasion of Panc-1 cells. These effects were reversed by Runx2 silencing. In conclusion, Runx2 is overexpressed in PDAC, where it is regulated by certain cytokines such as TGF-b1 and BMP2 in an auto-and paracrine manner. In addition, Runx2 has the potential to regulate the transcription of extracellular matrix modulators such as SPARC and MMP1, thereby influencing the tumour microenvironment.

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Fibroblast Growth Factor 2 Induction of the Osteocalcin Gene Requires MAPK Activity and Phosphorylation of the Osteoblast Transcription Factor, Cbfa1/Runx2

Cited by 358 publications

References 49 publications

Indian hedgehog: Its roles and regulation in endochondral bone development

Indian hedgehog: Its roles and regulation in endochondral bone development

Advanced Oxidation Protein Products Induce Vascular Calcification by Promoting Osteoblastic Trans-Differentiation of Smooth Muscle Cells via Oxidative Stress and ERK Pathway

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

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