Ras-MAPK Signaling in Osteogenic Differentiation: Friend or Foe?

Schindeler, Aaron; Little, David

doi:10.1359/jbmr.060603

Cited by 114 publications

(100 citation statements)

References 59 publications

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“…The physiologic roles of Erk activation in osteoblast differentiation also remain controversial and contradictory results have been observed, depending on the differential cell context or cell culture systems (40)(41)(42). A recent report showed that the cellular kinase activity of Erk1/2 was significantly downregulated during the differentiation of MC-3T3-E1 osteoblasts cultured for 7 days in the presence of ascorbic acid and b-glycerophosphate, which we used in our osteogenic culture system (43).…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor-2 Is an Important Factor that Maintains Cellular Immaturity and Contributes to Aggressiveness of Osteosarcoma

Shimizu

Ishikawa

Iwai

et al. 2012

Molecular Cancer Research

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Osteosarcoma is the most frequent, nonhematopoietic, primary malignant tumor of bone. Histopathologically, osteosarcoma is characterized by complex mixtures of different cell types with bone formation. The role of environmental factors in the formation of such a complicated tissue structure as osteosarcoma remains to be elucidated. Here, a newly established murine osteosarcoma model was used to clarify the roles of environmental factors such as fibroblast growth factor-2 (Fgf2) or leukemia-inhibitory factor (Lif) in the maintenance of osteosarcoma cells in an immature state. These factors were highly expressed in tumor environmental stromal cells, rather than in osteosarcoma cells, and they potently suppressed osteogenic differentiation of osteosarcoma cells in vitro and in vivo. Further investigation revealed that the hyperactivation of extracellular signal-regulated kinase (Erk)1/2 induced by these factors affected in the process of osteosarcoma differentiation. In addition, Fgf2 enhanced both proliferation and migratory activity of osteosarcoma cells and modulated the sensitivity of cells to an anticancer drug. The results of the present study suggest that the histology of osteosarcoma tumors which consist of immature tumor cells and pathologic bone formations could be generated dependent on the distribution of such environmental factors. The combined blockade of the signaling pathways of several growth factors, including Fgf2, might be useful in controlling the aggressiveness of osteosarcoma. Mol Cancer Res; 10(3); 454-68. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor-2 Is an Important Factor that Maintains Cellular Immaturity and Contributes to Aggressiveness of Osteosarcoma

Shimizu

Ishikawa

Iwai

et al. 2012

Molecular Cancer Research

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“…3). Various osteogenic stimuli, including BMP2, are known to induce the expression of osteomarkers (ALP, OPN, OCN, and so on) along with the activation of MAPK signaling molecules [12]. The activation of ERK and JNK, but not of p38, is necessary for the hNELL1-VH-induced OPN expression.…”

Section: Effects Of Ras Sirna On Opn Expressionmentioning

confidence: 99%

Involvement of MAPK signaling molecules and Runx2 in the NELL1‐induced osteoblastic differentiation

Bokui

Otani²,

Igarashi³

et al. 2007

FEBS Letters

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NELL1 is an extracellular protein inducing osteogenic differentiation and bone formation of osteoblastic cells. To elucidate the intracellular signaling cascade evoked by NELL1, we have shown that NELL1 protein transiently activates the MAPK signaling cascade, induces the phosphorylation of Runx2, and promotes the rapid intracellular accumulation of Tyr-phosphorylated proteins. Unlike BMP2, NELL1 protein does not activate the Smad signaling cascade. These findings suggest that upon binding to a specific receptor NELL1 transduces an osteogenic signal through activation of certain Tyrkinases associated with the Ras-MAPK cascade, and finally leads to the osteogenic differentiation.

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“…The signal transduction of Ras to ERK 1/2 is part of the NRF2-mediated oxidative stress response pathway analysed in this study (Table 2) [64]. Immunoblot analyses revealed the phosphorylation MSC were expanded and osteogenic or adipogenic differentiation was induced in the absence or presence of SNP.…”

Section: Discussionmentioning

confidence: 64%

Nitric Oxide Activates Signaling by c-Raf, MEK, p-JNK, p38 MAPK and p53 in Human Mesenchymal Stromal Cells inhibits their Osteogenic Differentiation by Blocking Expression of Runx2

Felka¹,

Ulrich²,

Rolauffs³

et al. 2014

J Stem Cell Res Ther

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Ras-MAPK Signaling in Osteogenic Differentiation: Friend or Foe?

Cited by 114 publications

References 59 publications

Fibroblast Growth Factor-2 Is an Important Factor that Maintains Cellular Immaturity and Contributes to Aggressiveness of Osteosarcoma

Fibroblast Growth Factor-2 Is an Important Factor that Maintains Cellular Immaturity and Contributes to Aggressiveness of Osteosarcoma

Involvement of MAPK signaling molecules and Runx2 in the NELL1‐induced osteoblastic differentiation

Nitric Oxide Activates Signaling by c-Raf, MEK, p-JNK, p38 MAPK and p53 in Human Mesenchymal Stromal Cells inhibits their Osteogenic Differentiation by Blocking Expression of Runx2

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