Core Binding Factor β Plays a Critical Role During Chondrocyte Differentiation

Park, Narae; Lim, Kyung-Eun; Han, Min-Su; Che, Xiangguo; Park, Clara Yongjoo; Kim, Jung-Eun; Taniuchi, Ichiro; Bae, Suk‐Chul; Choi, Je‐Yong

doi:10.1002/jcp.25068

Cited by 31 publications

(41 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We examined the impact of chondrocytes in new vessel formation during fracture healing in experimental Col2α1Cre + .FOXO1 L/L (Cre + ) mice with FOXO1 deletion and control Col2α1Cre – .FOXO1 L/L (Cre – ) littermates without FOXO1 deletion. The Col2α1Cre transgene has been shown to specifically delete several floxed genes in chondrocytes but no other cell types . Col2α1‐driven Cre recombinase deleted FOXO1 determined by genotyping (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Chondrocytes Promote Vascularization in Fracture Healing Through a FOXO1-Dependent Mechanism

Zhang¹,

Feinberg²,

Alharbi³

et al. 2018

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Chondrocytes play an essential role in fracture healing by producing cartilage, which forms an anlage for endochondral ossification that stabilizes the healing fracture callus. More recently it has been appreciated that chondrocytes have the capacity to produce factors that may affect the healing process. We examined the role of chondrocytes in angiogenesis during fracture healing and the role of the transcription factor forkhead box‐O 1 (FOXO1), which upregulates wound healing in soft tissue. Closed fractures were induced in experimental mice with lineage‐specific FOXO1 deletion by Cre recombinase under the control of a collagen‐2α1 promoter element (Col2α1Cre+FOXO1L/L) and Cre recombinase negative control littermates containing flanking loxP sites (Col2α1Cre–FOXO1L/L). Experimental mice had significantly reduced CD31+ new vessel formation. Deletion of FOXO1 in chondrocytes in vivo suppressed the expression of vascular endothelial growth factor‐A (VEGFA) at both the protein and mRNA levels. Overexpression of FOXO1 in chondrocytes in vitro increased VEGFA mRNA levels and VEGFA transcriptional activity whereas silencing FOXO1 reduced it. Moreover, FOXO1 interacted directly with the VEGFA promoter and a deacetylated FOXO1 mutant enhanced VEGFA expression whereas an acetylated FOXO1 mutant did not. Lastly, FOXO1 knockdown by siRNA significantly reduced the capacity of chondrocytes to stimulate microvascular endothelial cell tube formation in vitro. The results indicate that chondrocytes play a key role in angiogenesis which is FOXO1 dependent and that FOXO1 in chondrocytes regulates a potent angiogenic factor, VEGFA. These studies provide new insight into fracture healing given the important role of vessel formation in the fracture repair process. © 2018 American Society for Bone and Mineral Research.

show abstract

Section: Resultsmentioning

confidence: 99%

“…The Col2a1Cre transgene has been shown to specifically delete several floxed genes in chondrocytes but no other cell types. (40)(41)(42)(43)(44) Col2a1-driven Cre recombinase deleted FOXO1 determined by genotyping ( Fig. 1A) and deleted FOXO1 in chondrocytes as determined by immunofluorescence with specific antibody to FOXO1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Chondrocytes Promote Vascularization in Fracture Healing Through a FOXO1-Dependent Mechanism

Zhang¹,

Feinberg²,

Alharbi³

et al. 2018

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…It was generally an activator of transcription in T-47D cells where its binding sites were enriched at DEGs promoters, but showed a less constant role in MDA-MB-231. Of note, CBFB has previously been found to influence BMP signaling in chondrocytes [36] and it has also been shown to have invasive properties in breast, prostate and ovarian cancer cells [37, 38]. …”

Section: Discussionmentioning

confidence: 99%

Integrated RNA-seq and DNase-seq analyses identify phenotype-specific BMP4 signaling in breast cancer

et al. 2017

View full text Add to dashboard Cite

BackgroundBone morphogenetic protein 4 (BMP4) plays an important role in cancer pathogenesis. In breast cancer, it reduces proliferation and increases migration in a cell line-dependent manner. To characterize the transcriptional mediators of these phenotypes, we performed RNA-seq and DNase-seq analyses after BMP4 treatment in MDA-MB-231 and T-47D breast cancer cells that respond to BMP4 with enhanced migration and decreased cell growth, respectively.ResultsThe RNA-seq data revealed gene expression changes that were consistent with the in vitro phenotypes of the cell lines, particularly in MDA-MB-231, where migration-related processes were enriched. These results were confirmed when enrichment of BMP4-induced open chromatin regions was analyzed. Interestingly, the chromatin in transcription start sites of differentially expressed genes was already open in unstimulated cells, thus enabling rapid recruitment of transcription factors to the promoters as a response to stimulation. Further analysis and functional validation identified MBD2, CBFB, and HIF1A as downstream regulators of BMP4 signaling. Silencing of these transcription factors revealed that MBD2 was a consistent activator of target genes in both cell lines, CBFB an activator in cells with reduced proliferation phenotype, and HIF1A a repressor in cells with induced migration phenotype.ConclusionsIntegrating RNA-seq and DNase-seq data showed that the phenotypic responses to BMP4 in breast cancer cell lines are reflected in transcriptomic and chromatin levels. We identified and experimentally validated downstream regulators of BMP4 signaling that relate to the different in vitro phenotypes and thus demonstrate that the downstream BMP4 response is regulated in a cell type-specific manner.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3428-1) contains supplementary material, which is available to authorized users.

show abstract

“…Taken together, studies on RUNX subunits and complementary studies on CBFB [51, 52] have pointed to key roles for RUNX TFs in ECs, GPCs, and ACCs.…”

Section: Beta-scaffold Transcription Factors With Minor Groove Conmentioning

confidence: 99%

Transcriptional control of chondrocyte specification and differentiation

Liu

Samsa

Zhou

et al. 2017

Seminars in Cell & Developmental Biology

145

112

View full text Add to dashboard Cite

A milestone in the evolutionary emergence of vertebrates was the invention of cartilage, a tissue that has key roles in modeling, protecting and complementing the bony skeleton. Cartilage is elaborated and maintained by chondrocytes. These cells derive from multipotent skeletal progenitors and they perform highly specialized functions as they proceed through sequential lineage commitment and differentiation steps. They form cartilage primordia, the primary skeleton of the embryo. They then transform these primordia either into cartilage growth plates, temporary drivers of skeletal elongation and endochondral ossification, or into permanent tissues, namely articular cartilage. Chondrocyte fate decisions and differentiated activities are controlled by numerous extrinsic and intrinsic cues, and they are implemented at the gene expression level by transcription factors. The latter are the focus of this review. Meritorious efforts from many research groups have led over the last two decades to the identification of dozens of key chondrogenic transcription factors. These regulators belong to all types of transcription factor families. Some have master roles at one or several differentiation steps. They include SOX9 and RUNX2/3. Others decisively assist or antagonize the activities of these masters. They include TWIST1, SOX5/6, and MEF2C/D. Many more have tissue-patterning roles and regulate cell survival, proliferation and the pace of cell differentiation. They include, but are not limited to, homeodomain-containing proteins and growth factor signaling mediators. We here review current knowledge of all these factors, one superclass, class, and family at a time. We then compile all knowledge into transcriptional networks. We also identify remaining gaps in knowledge and directions for future research to fill these gaps and thereby provide novel insights into cartilage disease mechanisms and treatment options.

show abstract

Core Binding Factor β Plays a Critical Role During Chondrocyte Differentiation

Cited by 31 publications

References 54 publications

Chondrocytes Promote Vascularization in Fracture Healing Through a FOXO1-Dependent Mechanism

Chondrocytes Promote Vascularization in Fracture Healing Through a FOXO1-Dependent Mechanism

Integrated RNA-seq and DNase-seq analyses identify phenotype-specific BMP4 signaling in breast cancer

Transcriptional control of chondrocyte specification and differentiation

Contact Info

Product

Resources

About