Platelet-derived growth factor receptor kinase inhibitor AG-1295 promotes osteoblast differentiation in MC3T3-E1 cells via the Erk pathway

Zhang, Yongying; Cui, Yazhou; Luan, Jing; Zhou, Xiaoyan; Zhang, Genglin; Han, Jinxiang

doi:10.5582/bst.2012.v6.3.130

Cited by 10 publications

(8 citation statements)

References 24 publications

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“…PDGF/PDGFR signaling is reported to be involved in the regulation of various cell functions, including osteogenesis and adult stem cell differentiation toward osteoblasts. In particular, it has been observed that the downregulation of PDGR α promotes osteogenic differentiation of MSCs through the BMP/smad signaling pathway [ 32 ], and the blocking of the PDGFR- β pathway markedly promotes osteoblast differentiation and matrix mineralization in mouse osteoblastic MC3T3-E1 cells [ 33 ]. Moreover, PDGFR- β inhibition increases the osteogenic differentiation of primary rat osteoblastic cells [ 34 ] and human MSCs [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

GM1 Ganglioside Promotes Osteogenic Differentiation of Human Tendon Stem Cells

Bergante

Creo

Piccoli

et al. 2018

Stem Cells International

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Gangliosides, the sialic acid-conjugated glycosphingolipids present in the lipid rafts, have been recognized as important regulators of cell proliferation, migration, and apoptosis. Due to their peculiar localization in the cell membrane, they modulate the activity of several key cell receptors, and increasing evidence supports their involvement also in stem cell differentiation. In this context, herein we report the role played by the ganglioside GM1 in the osteogenic differentiation of human tendon stem cells (hTSCs). In particular, we found an increase of GM1 levels during osteogenesis that is instrumental for driving the process. In fact, supplementation of the ganglioside in the medium significantly increased the osteogenic differentiation capability of hTSCs. Mechanistically, we found that GM1 supplementation caused a reduction in the phosphorylation of the platelet-derived growth factor receptor-β (PDGFR-β), which is a known inhibitor of osteogenic commitment. These results were further corroborated by the observation that GM1 supplementation was able to revert the inhibitory effects on osteogenesis when the process was inhibited with exogenous PDGF.

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Section: Discussionmentioning

confidence: 99%

GM1 Ganglioside Promotes Osteogenic Differentiation of Human Tendon Stem Cells

Bergante

Creo

Piccoli

et al. 2018

Stem Cells International

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“…Inhibition of MAPK cascade at the level of growth factor receptor, MEK-1 or ERK leads to an increased differentiation of osteoblasts in different models as primary calvaria-derived osteoblasts or in pre-osteoblastic cell lines [28], [29]. It is known that PMT induces mitogenic signaling via MAPK-pathway in various cell lines as rat fibroblasts or HEK293 cells [13], [21].…”

Section: Discussionmentioning

confidence: 99%

“…However, the data available are inconsistent, because studies provide evidence for positive as well as for negative effects on bone cell development upon MAPK activation [28]–[31].…”

Section: Introductionmentioning

confidence: 99%

Pasteurella Multocida Toxin Prevents Osteoblast Differentiation by Transactivation of the MAP-Kinase Cascade via the Gαq/11 - p63RhoGEF - RhoA Axis

et al. 2013

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The 146-kDa Pasteurella multocida toxin (PMT) is the main virulence factor to induce P. multocida-associated progressive atrophic rhinitis in various animals. PMT leads to a destruction of nasal turbinate bones implicating an effect of the toxin on osteoblasts and/or osteoclasts. The toxin induces constitutive activation of Gα proteins of the Gq/11-, G12/13- and Gi-family by deamidating an essential glutamine residue. To study the PMT effect on bone cells, we used primary osteoblasts derived from rat calvariae and stromal ST-2 cells as differentiation model. As marker of functional osteoblasts the expression and activity of alkaline phosphatase, formation of mineralization nodules or expression of specific transcription factors as osterix was determined. Here, we show that the toxin inhibits differentiation and/or function of osteoblasts by activation of Gαq/11. Subsequently, Gαq/11 activates RhoA via p63RhoGEF, which specifically interacts with Gαq/11 but not with other G proteins like Gα12/13 and Gαi. Activated RhoA transactivates the mitogen-activated protein (MAP) kinase cascade via Rho kinase, involving Ras, MEK and ERK, resulting in inhibition of osteoblast differentiation. PMT-induced inhibition of differentiation was selective for the osteoblast lineage as adipocyte-like differentiation of ST-2 cells was not hampered. The present work provides novel insights, how the bacterial toxin PMT can control osteoblastic development by activating heterotrimeric G proteins of the Gαq/11-family and is a molecular pathogenetic basis for understanding the role of the toxin in bone loss during progressive atrophic rhinitis induced by Pasteurella multocida.

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“…An aliquot of MV pellets was lysed by addition of 100 μL buffer containing 25 mM Tris-HCl (pH = 7.4) and 0.5% Triton X-100 (15). Then, 1 μL of MVs lysate was mixed with 100 μL p-NPP.…”

Section: Alkaline Phosphatase Activity Analysismentioning

confidence: 99%

Label-free quantification proteomics reveals novel calcium binding proteins in matrix vesicles isolated from mineralizing Saos-2 cells

2013

Biosci Trends

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Platelet-derived growth factor receptor kinase inhibitor AG-1295 promotes osteoblast differentiation in MC3T3-E1 cells via the Erk pathway

Cited by 10 publications

References 24 publications

GM1 Ganglioside Promotes Osteogenic Differentiation of Human Tendon Stem Cells

GM1 Ganglioside Promotes Osteogenic Differentiation of Human Tendon Stem Cells

Pasteurella Multocida Toxin Prevents Osteoblast Differentiation by Transactivation of the MAP-Kinase Cascade via the Gαq/11 - p63RhoGEF - RhoA Axis

Label-free quantification proteomics reveals novel calcium binding proteins in matrix vesicles isolated from mineralizing Saos-2 cells

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