Wnt signalling mediates the cross-talk between bone marrow derived pre-adipocytic and pre-osteoblastic cell populations

Taipaleenmäki, Hanna; Abdallah, Basem M.; Aldahmash, Abdullah; Säämänen, Anna‐Marja; Kassem, Moustapha

doi:10.1016/j.yexcr.2010.12.015

Cited by 103 publications

(88 citation statements)

References 57 publications

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“…Conversely, osteogenic differentiation can be inhibited by the activation of protein kinase A, which upregulates peroxisome proliferatoractivated receptor gamma 2 (PPARg2) and in turn inhibits runtrelated transcription factor 2 (RUNX2) and osteopontin (OP), promoting adipogenesis [8]. RUNX2, a key lineage specific transcription factor, and signaling pathway molecules such as WNT and bone morphogenic protein (BMP) play a critical role in dictating MSC osteogenic differentiation [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel EZH2 Targets Regulating Osteogenic Differentiation in Mesenchymal Stem Cells

Hemming

Cakouros

Vandyke

et al. 2016

Stem Cells and Development

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Histone three lysine 27 (H3K27) methyltransferase enhancer of zeste homolog 2 (EZH2) is a critical epigenetic modifier, which regulates gene transcription through the trimethylation of the H3K27 residue leading to chromatin compaction and gene repression. EZH2 has previously been identified to regulate human bone marrow-derived mesenchymal stem cells (MSC) lineage specification. MSC lineage specification is regulated by the presence of EZH2 and its H3K27me3 modification or the removal of the H3K27 modification by lysine demethylases 6A and 6B (KDM6A and KDM6B). This study used a bioinformatics approach to identify novel genes regulated by EZH2 during MSC osteogenic differentiation. In this study, we identified the EZH2 targets, ZBTB16, MX1, and FHL1, which were expressed at low levels in MSC. EZH2 and H3K27me3 were found to be present along the transcription start site of their respective promoters. During osteogenesis, these genes become actively expressed coinciding with the disappearance of EZH2 and H3K27me3 on the transcription start site of these genes and the enrichment of the active H3K4me3 modification. Overexpression of EZH2 downregulated the transcript levels of ZBTB16, MX1, and FHL1 during osteogenesis. Small interfering RNA targeting of MX1 and FHL1 was associated with a downregulation of the key osteogenic transcription factor, RUNX2, and its downstream targets osteopontin and osteocalcin. These findings highlight that EZH2 not only acts through the direct regulation of signaling modules and lineage-specific transcription factors but also targets many novel genes important for mediating MSC osteogenic differentiation.

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Section: Introductionmentioning

confidence: 99%

Identification of Novel EZH2 Targets Regulating Osteogenic Differentiation in Mesenchymal Stem Cells

Hemming

Cakouros

Vandyke

et al. 2016

Stem Cells and Development

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“…Canonical and non-canonical Wnts are involved in determining whether MSCs differentiate into osteocytes or adipocytes. 135,136 FGF was demonstrated to increase osteogenesis via FGFR1 and 2, which activate the PI3K/Akt and Erk1/2 pathways. 137 The role of the interaction of multiple signal pathways in MSC differentiation has also been studied.…”

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confidence: 99%

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

Chen

Crawford

Chen

et al. 2013

Tissue Engineering Part B: Reviews

195

148

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Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and have been widely used in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway. MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway.

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“…[79,80] For instance, b-catenin knockout within the preosteoblasts of mice resulted in an increase in bone marrow adiposity and a decreased bone mass. [83] Wnt-3a is documented to be an inducer of Wnt signalling so that culturing mouse BMSC-derived preadipocyte and preosteoblast cells in a Wnt-3a conditioned medium led to the induction of the Wnt pathway and upregulation of the TCF/LEF gene within preosteoblasts. [82,83] Wnt signalling, however, did not occur to the same extent within the BMSC-derived preadipocytes and was instead characterised by the presence of the secreted frizzled-related protein 1 (sFRP-1), a competitive inhibitor of Wnt signalling.…”

Section: Signalling Pathways In Osteoblastogenesismentioning

confidence: 99%

“…[83] Wnt-3a is documented to be an inducer of Wnt signalling so that culturing mouse BMSC-derived preadipocyte and preosteoblast cells in a Wnt-3a conditioned medium led to the induction of the Wnt pathway and upregulation of the TCF/LEF gene within preosteoblasts. [82,83] Wnt signalling, however, did not occur to the same extent within the BMSC-derived preadipocytes and was instead characterised by the presence of the secreted frizzled-related protein 1 (sFRP-1), a competitive inhibitor of Wnt signalling. [83,84] sFRP-1 does so via binding to Wnt ligands Wnt-1 and Wnt-2 and to frizzled receptors, forming non-functional complexes that disrupt Wnt signalling.…”

Section: Signalling Pathways In Osteoblastogenesismentioning

confidence: 99%

Transdifferentiation of adipocytes to osteoblasts: potential for orthopaedic treatment

Lin

Dass

2018

Journal of Pharmacy and Pharmacology

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Objectives As both adipocytes and osteoblasts originate from the same pool of mesenchymal stem cells, increasing clinical evidence has emerged of the plasticity between the two lineages. For instance, the downregulation of osteoblast differentiation and upregulation of adipogenesis are common features of conditions such as multiple myeloma, obesity and drug-induced bone loss in diabetes mellitus. However, despite in-vitro and in-vivo observations of adipocyte transdifferentiation into osteoblasts, little is known of the underlying mechanisms. Key findings This review summarises the current knowledge of this particular transdifferentiation process whereby the Wnt/b-catenin signalling pathway and Runx2 overexpression have been postulated to play a critical role. Summary Furthermore, due to the possibility of a novel therapy in the treatment of bone conditions, a number of agents with the potential to induce adipo-toosteoblast transdifferentiation have been investigated such as all-trans retinoic acid, bone morphogenetic protein-9 and vascular endothelial growth factor.

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Wnt signalling mediates the cross-talk between bone marrow derived pre-adipocytic and pre-osteoblastic cell populations

Cited by 103 publications

References 57 publications

Identification of Novel EZH2 Targets Regulating Osteogenic Differentiation in Mesenchymal Stem Cells

Identification of Novel EZH2 Targets Regulating Osteogenic Differentiation in Mesenchymal Stem Cells

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

Transdifferentiation of adipocytes to osteoblasts: potential for orthopaedic treatment

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