Inhibition of methylation decreases osteoblast differentiation via a non-DNA-dependent methylation mechanism

Vaes, Bart; Lute, Carolien; Woning, Sebastian P. van der; Piek, Ester; Vermeer, Jenny A.F.; Blom, Henk J.; Mathers, John C.; Müller, Michael; Groot, Lisette C. P. G. M. de; Steegenga, Wilma T.

doi:10.1016/j.bone.2009.09.033

Cited by 35 publications

(24 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Folate could have an indirect role on bone remodelling cells via its metabolic link (as a methyl source) to the methylation of DNA, proteins and other molecules and there is evidence, albeit somewhat inconsistent, to support a reduced methylation capacity as a pathomechanism responsible for poor bone health (57,(72)(73)(74) . Alternatively, folate may exert a protective effect on bone through its homocysteine lowering effect (54) .…”

Section: Evidence To Support An Effect Of Homocysteine On Bonementioning

confidence: 99%

B-vitamins and bone in health and disease: the current evidence

et al. 2014

View full text Add to dashboard Cite

Osteoporosis, a metabolic skeletal disease characterised by decreased bone mass and increased fracture risk, is a growing public health problem. Among the various risk factors for osteoporosis, calcium and vitamin D have well-established protective roles, but it is likely that other nutritional factors are also implicated. This review will explore the emerging evidence supporting a role for certain B-vitamins, homocysteine and the 677C→T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase, in bone health and disease. The evidence, however, is not entirely consistent and as yet no clear mechanism has been defined to explain the potential link between B-vitamins and bone health. Coeliac disease, a common condition of malabsorption, induced by gluten ingestion in genetically susceptible individuals, is associated with an increased risk both of osteoporosis and inadequate B-vitamin status. Given the growing body of evidence linking low bone mineral density and/or increased fracture risk with low B-vitamin status and elevated homocysteine, optimal B-vitamin status may play an important protective role against osteoporosis in coeliac disease; to date, no trial has addressed this possible link.

show abstract

Section: Evidence To Support An Effect Of Homocysteine On Bonementioning

confidence: 99%

B-vitamins and bone in health and disease: the current evidence

et al. 2014

View full text Add to dashboard Cite

show abstract

“…SETDB1), Runx2, and HDAC4 represses Runx2 responsive genetic programs that regulate terminal chondrocyte differentiation during endochondral ossification, and mesenchymal ESET-deficient mice display premature chondrocyte hypertrophy, lower levels of trabecular bone formation, and defective expression of mineralization markers in long bones (81). Although it has yet to be determined whether direct methylation of Runx2 affects its function, inhibition of SAM methyltransferases in C2C12 stromal cells attenuated BMP2-induced activation of Runx2 (78). This effect was not observed in response to a specific reduction in DNA methylation, suggesting that methylation cycling at the protein level is necessary for Runx2 transcriptional activation.…”

Section: Inhibition Of Oga Increases Alp Expression and Activity Inmentioning

confidence: 99%

O-GlcNAc Modification of the runt-Related Transcription Factor 2 (Runx2) Links Osteogenesis and Nutrient Metabolism in Bone Marrow Mesenchymal Stem Cells

Nagel

Ball

2014

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Runx2 [also known as: core binding factor ␣ 1 (CBFA1); acute myeloid leukemia transcription factor 3 (AML3); polyoma enhancer-binding protein 2␣ (PEPB2␣)] is a member of the runt-domain gene family of DNA binding proteins (Runx1, Runx2, and Runx3), which control the expression of numerous genes involved in cell growth, proliferation, and determination of cell lineage (1). Aberrant expression and activity of Runx proteins are implicated in leukemia, metastatic breast cancer, and defects in skeletal development and bone remodeling (2-4). Runx2 is expressed during early embryonic development in mesenchymal and cartilage condensations of the developing bone anlagen, and its transcription, activity, and stability are tightly regulated (5-7). Considered the master regulator of osteoblast differentiation, Runx2 also contributes to chondrocyte maturation (8,9) and, through these cell-types, controls intramembranous and endochondral ossification culminating in the formation of the mineralized skeleton (5, 6, 10). A gain-of-function mutation of Runx2, resulting from duplication of exons 3 to 5, is linked to dysplastic long bone formation, enlarged clavicles, and thickening of the cranial vault (11). Conversely, the rare autosomal dominant disorder, cleidocranial dysplasia, has been traced to multiple loss-of-function mutations within the Cbfa1 gene, and is characterized by defective formation or absence of the clavicle, enlarged fontanelles, and dental abnormalities (9, 12, 13). Mice nullizygous for Runx2 develop a cartilaginous skeletal framework that fails to undergo mineralization caused by the absence of osteoblasts, and these mice die at birth because of respiratory failure (5, 10).

show abstract

“…We pretreated the cells with 5-AZA to inhibit DNA methylation, which has been recognized in important differentiation processes, such as osteoblast (Vaes et al 2009), cardiomycyte (Tomita et al 1999) and more recently pancreatic endocrine differentiation (Lefebvre et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Differentiation of nestin-positive cells derived from bone marrow into pancreatic endocrine and ductal cells in vitro

Milanesi

Lee²,

Xu³

et al. 2011

Journal of Endocrinology

View full text Add to dashboard Cite

Promising results of pancreatic islet transplantation to treat type 1 diabetes mellitus, combined with severe shortage of donor pancreata, have spurred efforts to generate pancreatic islet-like cells and insulin-producing b-cells from various progenitor populations. In this study, we show for the first time that multipotent nestin-positive stem cells selected from rat bone marrow can be differentiated into pancreatic ductal and insulin-producing b-cells in vitro. We report an effective multistep protocol in a serum-free system, which could efficiently induce b-cell differentiation from multipotent nestin-positive bone marrow stem cells. To enhance the induction and differentiation toward pancreatic lineage we used trichostatin A, an important regulator of chromatin remodeling, and 5-aza 2 0 deoxycytidine, an inhibitor of DNA methylase. All-trans retinoic acid was then utilized to promote pancreatic differentiation. We sequentially induced important transcription factor genes, such as Pdx1, Ngn3, and Pax6, following the in vivo development timeline of the pancreas in rats. Furthermore, in the final stage with the presence of nicotinamide, the induced cells expressed islet and ductal specific markers. The differentiated cells not only expressed insulin and glucose transporter 2, but also displayed a glucoseresponsive secretion of the hormone. Our results delineate a new model system to study islet neogenesis and possible pharmaceutical targets. Nestin-positive bone marrow stem cells may be therapeutically relevant for b-cell replacement in type 1 diabetes.

show abstract

Inhibition of methylation decreases osteoblast differentiation via a non-DNA-dependent methylation mechanism

Cited by 35 publications

References 46 publications

B-vitamins and bone in health and disease: the current evidence

B-vitamins and bone in health and disease: the current evidence

O-GlcNAc Modification of the runt-Related Transcription Factor 2 (Runx2) Links Osteogenesis and Nutrient Metabolism in Bone Marrow Mesenchymal Stem Cells

Differentiation of nestin-positive cells derived from bone marrow into pancreatic endocrine and ductal cells in vitro

Contact Info

Product

Resources

About