SOXC proteins amplify canonical WNT signaling to secure nonchondrocytic fates in skeletogenesis

Bhattaram, Pallavi; Penzo–Méndez, Alfredo; Kato, Kenji; Bandyopadhyay, Kaustav; Gadi, Abhilash; Taketo, Makoto Mark; Lefebvre, Véronique

doi:10.1083/jcb.201405098

Cited by 68 publications

(84 citation statements)

References 49 publications

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“…SOX4, SOX11, and SOX12 (SOXC proteins) are closely related to one another, but not to SOX8/9 and SOX5/6. They are expressed strongly in SSCs and PCs, and weakly in chondrocytes [34]. They act redundantly to keep SSCs alive and they critically help delineate cartilage primordia by securing the non-chondrocytic fate of perichondrium cells and JPs [34, 35].…”

Section: Beta-scaffold Transcription Factors With Minor Groove Conmentioning

confidence: 99%

“…They are expressed strongly in SSCs and PCs, and weakly in chondrocytes [34]. They act redundantly to keep SSCs alive and they critically help delineate cartilage primordia by securing the non-chondrocytic fate of perichondrium cells and JPs [34, 35]. They are also pivotal to initiate GP formation through actions both in perichondrium cells and in GPCs [36].…”

Section: Beta-scaffold Transcription Factors With Minor Groove Conmentioning

confidence: 99%

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Transcriptional control of chondrocyte specification and differentiation

Liu

Samsa

Zhou

et al. 2017

Seminars in Cell & Developmental Biology

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145

112

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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.

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Section: Beta-scaffold Transcription Factors With Minor Groove Conmentioning

confidence: 99%

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

Self Cite

145

112

View full text Add to dashboard Cite

show abstract

“…It is well established that β-catenin and SOX9 directly antagonize each other’s stability in differentiating chondrocytes [59] [60] [61] [62] [63]. The inactivation of β-catenin specifically in chondrocytes of mouse embryos led to severe dwarfism with decreased chondrocyte proliferation, delayed hypertrophy, and impaired endochondral bone formation accompanied by increased Sox9 expression [59].…”

Section: Wnt/β-catenin Signalingmentioning

confidence: 99%

Signaling pathways regulating cartilage growth plate formation and activity

Samsa

Zhou

2017

Seminars in Cell & Developmental Biology

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The growth plate is a highly specialized and dynamic cartilage structure that serves many essential functions in skeleton patterning, growth and endochondral ossification in developing vertebrates. Major signaling pathways initiated by classical morphogens and by other systemic and tissuespecific factors are intimately involved in key aspects of growth plate development. As a corollary of these essential functions, disturbances in these pathways due to mutations or environmental factors lead to severe skeleton disorders. Here, we review these pathways and the most recent progress made in understanding their roles in chondrocyte differentiation in growth plate development and activity. Furthermore, we discuss newly uncovered pathways involved in growth plate formation, including mTOR, the circadian clock, and the COP9 signalosome.

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“…In terms of skeletal homeostasis and bone repair, the Wnt pathway is among the most attractive targets for such therapeutic interventions. There is now a substantial literature supporting the role of Wnt signaling in skeletogenesis and a growing appreciation for the functions of Wnt in regulating stem cell and skeletal cell behaviors [6,7]. Reports show that Wnt signals regulate bone mass by perpetuating the self-renewal and proliferation of stem cells and inducing differentiation of osteoprogenitor cells [8,9].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-10a Influences Osteoblast Differentiation and Angiogenesis by Regulating β-Catenin Expression

Zhang

Zhao

et al. 2015

Cell Physiol Biochem

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Background/Aims: Elucidation of the molecular mechanisms governing osteoblast differentiation and angiogenesis are of great importance for improving the treatment of bone-related diseases. In this study, we examined the role of microRNA (miR)-10a in the differentiation of MC3T3-E1 cells and pro angiogenic activity of mouse umbilical vein endothelial cells (MUVECs). Methods: The murine pre-osteoblast cell line MC3T3-E1 and MUVECs were used in the experiment. After transfected with miR-10a mimics or inhibitors, with or without LiCl pretreatment, the miR-10a, ALP, Runx2, Osx, OC and Dlx5 expression were assessed by RT-PCR. MC3T3-E1 cells were cultured with BMP2 to differentiate into bone cells, osteogenic differentiation of MC3T3-E1 cells were detected by ALP and ARS staining. Cell viability were analyzed by MTT and the protein expression of β-catenin, LEF1, cyclinD1, MMP2, and VEGF were detected by Western blotting; VEGF and VE-cadherin release were assessed by ELISA, and the migration of MUVECs, as well as tube formation were also detected. Results: MiR-10a expression was obviously down-regulated during osteogenic differentiation. Overexpression of miR-10a inhibited osteogenic differentiation of MC3T3-E1 cells, effectively decreasing MUVECs proliferation, migration, VEGF expression, VE-cadherin concentrations, and tube formation in vitro, whereas miR-10a silence enhanced those processes. Further mechanism assays demonstrated that overexpression of miR-10a reduced the β-catenin at both protein and transcription level, while pretreatment with Wnt signaling activator Licl partially attenuated the suppression effects of miR-10a overexpression on osteoblast differentiation and angiogenesis. Conclusion: Our findings imply that miR-10a plays a suppressive role in osteoblast differentiation of MC3T3-E1 cells and pro angiogenic activity of MUVECs by regulating the β-catenin expression, representing a novel and potential therapeutic target for the treatment of bone regeneration-related diseases.

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SOXC proteins amplify canonical WNT signaling to secure nonchondrocytic fates in skeletogenesis

Abstract: In skeletogenic mesenchyme, SOXC proteins enter the APC–Axin destruction complex to inhibit β-catenin phosphorylation by GSK3 and thereby synergize with canonical WNT signaling to inhibit chondrogenesis.

Cited by 68 publications

References 49 publications

Transcriptional control of chondrocyte specification and differentiation

Transcriptional control of chondrocyte specification and differentiation

Signaling pathways regulating cartilage growth plate formation and activity

MicroRNA-10a Influences Osteoblast Differentiation and Angiogenesis by Regulating β-Catenin Expression

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