Journal ArticleDOI
Activation of p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase by BMP-2 and their implication in the stimulation of osteoblastic cell differentiation.
Jérôme Guicheux,J Lemonnier,J Lemonnier,Chafik Ghayor,Atsushi Suzuki,Atsushi Suzuki,Gaby Palmer,Joseph Caverzasio +7 more
TLDR
It is reported that BMP‐2 can activate JNK and p38 in osteoblastic cells and evidence is provided that these MAP kinases have distinct roles in regulating alkaline phosphatase and osteocalcin expression.Abstract:
Signaling involved in osteoblastic cell differentiation remains largely unknown. This study further investigates mechanisms involved in BMP-2-induced osteoblastic cell differentiation. We report that BMP-2 can activate JNK and p38 in osteoblastic cells and provide evidences that these MAP kinases have distinct roles in regulating alkaline phosphatase and osteocalcin expression.
Introduction: Bone morphogenetic protein (BMP)-2 exerts many of its biological effects through activation of the Smad pathway. Cooperative interactions between the Smads and the stress-activated protein kinase (SAPK) p38 and c-Jun-NH2-terminal kinase (JNK) pathways have recently been observed in TGF-β signaling.
Materials and Methods: Activation of mitogen-activated protein (MAP) kinases by BMP-2 and the role of these signaling pathways for cell differentiation induced by BMP-2 was investigated in mouse MC3T3-E1 and primary cultured calvaria-derived osteoblastic cells using immunoprecipitation, in vitro kinase assay and Western blot analysis, as well as specific MAP kinase inhibitors.
Results: Associated with the rapid activation of Smads, BMP-2 barely affected extracellular-signal regulated kinase (ERK) activity, whereas it induced a transient activation of p38 and JNK. The role of p38 and JNK in mediating BMP-2-induced stimulation of osteoblastic cell differentiation was evaluated using the respective specific inhibitors SB203580 and SP600125. Inhibition of p38 by SB203580 was mainly associated with decreased alkaline phosphatase (ALP) activity, whereas inhibition of JNK by SP600125 was associated with a marked reduction in osteocalcin (OC) production induced by BMP-2. Corresponding alterations in ALP and OC mRNA levels were found in cells treated with BMP-2 and inhibitors, suggesting an implication of p38 and JNK pathways in BMP-2-induced osteoblastic cell differentiation at a transcriptional level.
Conclusion: Data presented in this study describe p38 and JNK as new signaling pathways involved in BMP-2-induced osteoblastic cell differentiation with evidences for a distinct role of each MAP kinase in the control of alkaline phosphatase and osteocalcin expression.read more
Citations
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Journal ArticleDOI
Non-Smad TGF-β signals
TL;DR: Non-Smad signal transducers under the control of TGF-β provide quantitative regulation of the signalling pathway, and serve as nodes for crosstalk with other major signalling pathways, such as tyrosine kinase, G-protein-coupled or cytokine receptors.
Journal ArticleDOI
Bone Morphogenetic Proteins: A critical review
TL;DR: This review focuses on the different levels of regulation, ranging from the release of BMPs into the extracellular components to receptor activation for different B MPs, and highlights areas in research that are lacking or contradictory.
Journal ArticleDOI
Signaling and transcriptional regulation in osteoblast commitment and differentiation.
TL;DR: This review summarizes the recent advances in the studies of signaling transduction pathways and transcriptional regulation of osteoblast cell lineage commitment and differentiation that enable a better understanding of the multiple factors and signaling networks that control the differentiation process at a molecular level.
Journal ArticleDOI
Networks and hubs for the transcriptional control of osteoblastogenesis
Jane B. Lian,Gary S. Stein,Amjad Javed,Andre J. van Wijnen,Janet L. Stein,Martin Montecino,Mohammad Q. Hassan,Tripti Gaur,Christopher J. Lengner,Daniel W. Young +9 more
TL;DR: An overview of the concepts of tissue-specific transcriptional control mechanisms essential for development of the bone cell phenotype is presented and the specificity of Runx2 regulatory activities provides a basis for novel therapeutic strategies to correct bone disorders.
Journal ArticleDOI
BMP signaling in skeletal development.
TL;DR: A review of BMP signaling pathways in the context of craniofacial, axial, and limb development will focus on recent advances of the role of different ligands, receptors, Smads, and BMP regulators in osteoblast and chondrocyte differentiation during embryonic development.
References
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Targeted Disruption of Cbfa1 Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts
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SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
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