p38 MAPK Signaling in Osteoblast Differentiation

Rodríguez-Carballo, Eddie; Gámez, Beatriz; Ventura, Francesc

doi:10.3389/fcell.2016.00040

Cited by 242 publications

(199 citation statements)

References 250 publications

(280 reference statements)

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“…The TGF-β/MAPK signaling pathway plays an important role in cell development, including differentiation, migration and proliferation [18]. ERK1/2 and ERK5, JNK1/2/3, and the p38 isoforms are members of the conventional MAPK family [19]. It was pointed out that ERK1/2 is activated by PI3K/Akt triggered by the binding of TGF-β with its receptors, indicating that TGF-β may induce MAPK proteins [20,21].…”

Section: Discussionmentioning

confidence: 99%

Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model

Wang

2017

Cell Physiol Biochem

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Background/Aims: This study aimed to explore the role of TGF-β in tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction using bone marrow-derived mesenchymal stem cells (BMSCs) through the TGF-β/MAPK signaling pathway in a New Zealand white rabbit model. Methods: A total of 72 healthy male New Zealand white rabbits were selected for these experiments. Flow cytometry and immunofluorescence were used to detect the expression of BMSC surface markers, and qRT-PCR was performed to detect TGF-β mRNA expression. The ACL reconstruction model was established with autografts. The rabbits were randomly divided into the following groups: inhibition of TGF-β (inhibition), over-expression of TGF-β (over-expression), empty vector and untreated (n = 18 per group). Hematoxylineosin (HE) staining, toluidine blue staining and Masson trichrome staining were conducted to observe any chondrocyte-like cell growth, and biomechanical tests were used to calculate the maximum load and rigidity. Three-dimensional CT imaging and Western blotting were applied to detect changes in bone tunnel size and bone density and the expression levels of TGF-β/MAPK signaling pathway-related proteins, respectively. Results: CD90 and CD44 were positively expressed, while CD11b was not detected. Compared with the empty vector and untreated groups, TGF-β mRNA expression was significantly decreased in the inhibition group but increased in the over-expression group; the latter group had a larger number of fibroblasts, a tighter tendon-bone interface, an increased number of chondrocyte-like cells and fibrochondrocytes, and more collagen fibers than the inhibition, empty vector and untreated groups. Compared with the empty vector and untreated groups, the maximum load and rigidity; the CT values of bone tunnel and bone tunnel margin; and the protein expression levels of TGF-β, p-ERK1/2, p-p38, p-JNK, c-jun and c-myc were significantly down-regulated in the inhibition group but up-regulated in the over-expression group. Conclusion: Our study indicated that up-regulating TGF-β expression in BMSCs from New Zealand white rabbits could promote tendon-to-bone healing after ACL reconstruction by regulating the TGF-β/MAPK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model

Wang

2017

Cell Physiol Biochem

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“…It was reported that the p38/MAPK and MAPK/ERK signaling pathways are related to PDLSC self-renewal (Bernet et al, 2014;Sun et al, 2015;Rodríguez-Carballo et al, 2016). Therefore, western blotting was performed to detect related protein expression in PDLSCs after hypoxic culture for 48 h ( Figure 5).…”

Section: Hypoxia Activates P38/mapk and Mapk/erk Signaling Pathways Imentioning

confidence: 99%

Hypoxia enhances periodontal ligament stem cell proliferation via the MAPK signaling pathway

He¹,

Cao²,

Zhang³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. There is high incidence of periodontal disease in highaltitude environments; hypoxia may influence the proliferation and clone-forming ability of periodontal ligament stem cells (PDLSCs). The MAPK signaling pathway is closely correlated with cell proliferation, differentiation, and apoptosis. Thus, we isolated and cultured PDLSCs under hypoxic conditions to clarify the impact of hypoxia on PDLSC proliferation and the underlying mechanism. PDLSCs were separated and purified by the limiting dilution method and identified by flow cytometry. PDLSCs were cultured under hypoxic or normoxic conditions to observe their cloning efficiency. PDLSC proliferation at different oxygen concentrations was evaluated by MTT assay. Expression of p38/MAPK and MAPK/ERK signaling pathway members was detected by western blotting. Inhibitors for p38/MAPK or ERK were applied to PDLSCs to observe their impacts on clone formation and proliferation. Isolated PDLSCs exhibited typical stem cell morphological characteristics, strong abilities of globular clone formation and proliferation, and upregulated expression of mesenchymal stem cell markers. Stem cell marker expression was not statistically different between PDLSCs cultured under hypoxia and normoxia (P > 0.05). The clone number in the hypoxia group was significantly higher than that in the control (P < 0.05). PDLSC proliferation under hypoxia was higher than that of the control (P < 0.001). p38 and ERK1/2 phosphorylation in hypoxic PDLSCs was markedly enhanced compared to that in the control (P < 0.05). Either P38/MAPK inhibitor or ERK inhibitor treatment reduced clone formation and proliferation. Therefore, hypoxia enhanced PDLSC clone formation and proliferation by activating the p38/MAPK and ERK/MAPK signaling pathways.

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“…We have previously demonstrated that TGF-β stimulates VEGF synthesis at least in part though the p38 MAP kinase activation in osteoblast-like MC3T3-E1 cells [28]. Nowadays, p38 MAP kinase is well recognized to be a crucial pathway in the TGF-β signaling in osteoblasts [29]. However, the exact mechanism behind TGF-β-induced VEGF synthesis in osteoblasts remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Heat Shock Protein 70 Negatively Regulates TGF-β-Stimulated VEGF Synthesis via p38 MAP Kinase in Osteoblasts

Sakai

Tokuda

Fujita

et al. 2017

Cell Physiol Biochem

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Background/Aims: We previously demonstrated that transforming growth factor-β (TGF-β) stimulates the synthesis of vascular endothelial growth factor (VEGF) through the activation of p38 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. Heat shock protein70 (HSP70) is a ubiquitously expressed molecular chaperone. In the present study, we investigated the involvement of HSP70 in the TGF-β-stimulated VEGF synthesis and the underlying mechanism in these cells. Methods: Culture MC3T3-E1 cells were stimulated by TGF-β. Released VEGF was measured using an ELISA assay. VEGF mRNA level was quantified by RT-PCR. Phosphorylation of each protein kinase was analyzed by Western blotting. Results: VER-155008 and YM-08, both of HSP70 inhibitors, significantly amplified the TGF-β-stimulated VEGF release. In addition, the expression level of VEGF mRNA induced by TGF-β was enhanced by VER-155008. These inhibitors markedly strengthened the TGF-β-induced phosphorylation of p38 MAP kinase. The TGF-β-induced phosphorylation of p38 MAP kinase was amplified in HSP70-knockdown cells. SB203580, an inhibitor of p38 MAP kinase, significantly suppressed the amplification by these inhibitors of the TGF-β-induced VEGF release. Conclusion: These results strongly suggest that HSP70 acts as a negative regulator in the TGF-β-stimulated VEGF synthesis in osteoblasts, and that the inhibitory effect of HSP70 is exerted at a point upstream of p38 MAP kinase.

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p38 MAPK Signaling in Osteoblast Differentiation

Cited by 242 publications

References 250 publications

Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model

Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model

Hypoxia enhances periodontal ligament stem cell proliferation via the MAPK signaling pathway

Heat Shock Protein 70 Negatively Regulates TGF-β-Stimulated VEGF Synthesis via p38 MAP Kinase in Osteoblasts

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