Evidence for a role of p38 MAP kinase in expression of alkaline phosphatase during osteoblastic cell differentiation

Suzuki, Atsushi; Guicheux, Jérôme; Palmer, Gaby; Miura, Yoshitaka; Oiso, Yutaka; Bonjour, J. P.; Caverzasio, Joseph

doi:10.1016/s8756-3282(01)00660-3

Cited by 170 publications

(158 citation statements)

References 41 publications

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“…(36) Essentially, cells were harvested in 0.1% Nonidet P-40 and disrupted by sonication. The homogenate was centrifuged at 1500g for 5 minutes, and ALP was determined by the method of Lowry and colleagues.…”

Section: Alkaline Phosphatase Activitymentioning

confidence: 99%

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Caverzasio

Thouverey

2012

Journal of Bone and Mineral Research

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Previous studies have shown that Wnt3a enhances the proliferation and inhibits the osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this study, we investigated the signaling pathways involved in Wnt3a-induced osteoblastic cell proliferation. Experiments with DKK1, a natural antagonist of Lrp5/6, indicated that Wnt/b-catenin did not play a major role in Wnt3a-induced osteoblastic cell proliferation. The use of selective inhibitors of known mitogenic pathways implicates Src family kinases (SFKs) and a protein kinase C (PKC) in this cellular response. Time-dependent analysis of signaling molecules activated by Wnt3a in MC3T3-E1 cells revealed parallel activation of the canonical pathway and of several tyrosine kinases, including SFKs and PDGF receptors (PDGF-Rs). Functional analysis with specific inhibitors suggested a major role of PDGF-Rs in mediating Wnt3a-induced cell proliferation. Further investigation with an si-RNA approach confirmed a predominant role of this receptor in this cellular response. The use of soluble decoy PDGF-Rs that can sequester extracellular PDGFs excluding that part of the increased PDGF receptor phosphorylation by Wnt3a was the result of autocrine production of PDGFs. A selective SFK inhibitor blunted the enhanced PDGF-R phosphorylation and cell proliferation induced by Wnt3a. Studies of initial events involved in the regulation of this pathway suggest a role of dishevelled. In conclusion, data presented in this study indicate that cell proliferation induced by Wnt3a in osteoblastic cells is mediated by a dishevelleddependent and b-catenin-independent pathway, which involves the transactivation of PDGF receptors. ß

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Section: Alkaline Phosphatase Activitymentioning

confidence: 99%

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Caverzasio

Thouverey

2012

Journal of Bone and Mineral Research

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“…25 Many studies demonstrated that p38 MAPK can promote osteogenic differentiation. 26,27 The MAPK signaling pathway also has been implicated in stem cell proliferation and differentiation induced by nanomaterials. Gold nanoparticles promoted the differentiation of MSCs toward osteoblast cells by activating the p38 MAPK signaling pathway.…”

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confidence: 99%

Graphene/single-walled carbon nanotube hybrids promoting osteogenic differentiation of mesenchymal stem cells by activating p38 signaling pathway

Yan¹,

Yang²,

Shao³

et al. 2016

IJN

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Carbon nanomaterials are becoming increasingly significant in biomedical fields since they exhibit exceptional physicochemical and biocompatible properties. Today, the stem cells offer potentially new therapeutic approaches in tissue engineering and regenerative medicine. However, the induction of differentiation into specific lineages remains challenging, which provoked us to explore the biomedical applications of carbon nanomaterials in stem cells. In this study, we investigated the interactions between graphene/single-walled carbon nanotube (G/SWCNT) hybrids and rat mesenchymal stem cells (rMSCs) and focused on the proliferation and differentiation of rMSCs treated with G/SWCNT hybrids. Cell viability and morphology were evaluated using cell counting kit-8 assay and immunofluorescence staining, respectively. Osteogenic differentiation evaluated by alkaline phosphatase activity of MSCs proved to be higher after treatment with G/SWCNT hybrids, and the mineralized matrix nodule formation was also enhanced. In addition, the expression levels of osteogenic-associated genes were upregulated, while the adipocyte-specific markers were downregulated. Consistent with these results, we illustrated that the effect of G/SWCNT hybrids on the process of osteogenic differentiation of rMSCs can be modulated by activating the p38 signaling pathway and inhibiting the extracellular signal-regulated kinase 1/2 pathway. Nevertheless, our study suggests that carbon nanomaterials offer a promising platform for regenerative medicine in the near future.

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“…Although ERK and p38 MAPKs both have been reported as regulating osteoblast differentiation, (30,31) we have shown that the BMP-2-induced osteogenesis of C3H10T1/2 and C2C12 cells, which specifically enhanced DDR2 expression among all collagen receptors, is associated with increased phosphorylation of p38 but not ERK. Furthermore, while inhibition of ERK activity does not affect DDR2-dependent OCN promoter activation, inhibition of either the expression or activation of p38 abolishes Fig.…”

Section: Discussionmentioning

confidence: 63%

Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic differentiation through p38 MAPK-mediated Runx2 activation

Lin

Chou

Hsieh

et al. 2010

Journal of Bone and Mineral Research

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Deficiency of the collagen receptor discoidin domain receptor tyrosine kinase (DDR2) in mice and humans results in dwarfism and short limbs, of which the mechanism remains unknown. Here we report that DDR2 is a key regulator of osteoblast differentiation. DDR2 mRNA expression was increased at an early stage of induced osteoblast differentiation. In the subchondral bone of human osteoarthritic knee, DDR2 was detected in osteoblastic cells. In mouse embryos, DDR2 expression was found from E11 to E15, preceding osteocalcin (OCN) and coinciding with Runx2 expression. Activating transcription factor 4 (ATF4) enhanced DDR2 mRNA expression, and knockdown of ATF4 expression delayed DDR2 induction during osteoblast differentiation. A CCAAT/enhancer binding protein (C/EBP) binding site at À1150 bp in the DDR2 promoter was required for ATF4-mediated DDR2 activation. C/EBPb bound to and cooperated with ATF4 in stimulating DDR2 transcription; accordingly, the ATF4 mutants deficient of C/EBPb binding were incapable of transactivating DDR2. Overexpression of DDR2 increased osteoblast-specific gene expression. Conversely, knockdown of DDR2 suppressed osteogenic marker gene expression and matrix mineralization during the induced osteogenesis. The stimulation of p38 MAPK by DDR2 was required for DDR2-induced activation of Runx2 and OCN promoters. Together our findings uncover a pathway in which ATF4, by binding to C/EBPb transcriptionally upregulates DDR2 expression, and DDR2, in turn, activates Runx2 through p38 MAPK to promote osteoblast differentiation. ß

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Evidence for a role of p38 MAP kinase in expression of alkaline phosphatase during osteoblastic cell differentiation

Cited by 170 publications

References 41 publications

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Graphene/single-walled carbon nanotube hybrids promoting osteogenic differentiation of mesenchymal stem cells by activating p38 signaling pathway

Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic differentiation through p38 MAPK-mediated Runx2 activation

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