NFIA and GATA3 are crucial regulators of embryonic articular cartilage differentiation

Singh, Pratik; Yadav, Upendra Singh; Azad, Kimi; Goswami, Pooja; Kinare, Veena; Bandyopadhyay, Amitabha

doi:10.1242/dev.156554

Cited by 22 publications

(18 citation statements)

References 45 publications

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“…The most commonly expressed genes specific to the Lgr5 + bulk dataset included transcription factors ( Glis1 , Barx2 , and Pknox2 ) and ECM proteins ( Cilp and Col22a1 ). Several transcription factors reported to be related to joint formation were either specifically or more strongly expressed in Lgr5 + cells from the digit joint, such as Gata3 (Singh et al., 2018), Barx1/2 (Makarenkova and Meech, 2012), Irx1/2 (Zulch et al., 2001), and Sox5/6 (Dy et al., 2010) (Figure S3E and Tables S1–S3). Known pathways regulating interzone differentiation such as WNT, TGFβ, and MAPK (Decker et al., 2014, Gunnell et al., 2010) are also enriched in our Lgr5 + dataset (Figure S3F and Table S4).…”

Section: Resultsmentioning

confidence: 99%

Lgr5 and Col22a1 Mark Progenitor Cells in the Lineage toward Juvenile Articular Chondrocytes

et al. 2019

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SummaryThe synovial joint forms from a pool of progenitor cells in the future region of the joint, the interzone. Expression of Gdf5 and Wnt9a has been used to mark the earliest cellular processes in the formation of the interzone and the progenitor cells. However, lineage specification and progression toward the different tissues of the joint are not well understood. Here, by lineage-tracing studies we identify a population of Lgr5+ interzone cells that contribute to the formation of cruciate ligaments, synovial membrane, and articular chondrocytes of the joint. This finding is supported by single-cell transcriptome analyses. We show that Col22a1, a marker of early articular chondrocytes, is co-expressed with Lgr5+ cells prior to cavitation as an important lineage marker specifying the progression toward articular chondrocytes. Lgr5+ cells contribute to the repair of a joint defect with the re-establishment of a Col22a1-expressing superficial layer.

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Section: Resultsmentioning

confidence: 99%

Lgr5 and Col22a1 Mark Progenitor Cells in the Lineage toward Juvenile Articular Chondrocytes

et al. 2019

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“…A recent research showed that NFIA is colocalized with peroxisome proliferators‐activated receptor γ and regulates the transcription of the brown fat genes (Hiraike et al, 2017). More recently, it was demonstrated that NFIA‐ and GATA‐binding protein 3 regulated the differentiation of embryonic articular cartilage in chick (Singh et al, 2018). In the current study, our results indicate that NFIA overexpression reduced ALP staining and downregulated the mRNA expression of osteogenic markers, indicating that NFIA negatively regulated osteoblast differentiation.…”

Section: Discussionmentioning

confidence: 99%

miR‐142a‐5p promoted osteoblast differentiation via targeting nuclear factor IA

Yuan

Xue

et al. 2020

Journal Cellular Physiology

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miR-142a-5p plays critical roles in multiple biological processes and diseases, such as inflammation and tumorigenesis. However, it remains to be explored if and how miR-142a-5p contributes to osteoblast differentiation. In this study, our results showed that miR-142a-5p was highly expressed in bone tissue of mice and increased during osteogenesis in preosteoblast MC3T3-E1 cells. Supplementing miR-142a-5p activity using miR-142a-5p agomir promoted osteogenic differentiation in stromal cell line ST2 and preosteoblastic line MC3T3-E1. Conversely, miR-142a-5p antagomir, an inhibitor of endogenous miR-142a-5p, could reduce osteoblast differentiation in ST2 and MC3T3-E1 cells. Nuclear factor IA (NFIA), a site-specific transcriptional factor, was demonstrated to be directly targeted by miR-142a-5p. Overexpression of NFIA inhibited miR-142a-5p-mediated osteoblast differentiation in ST2 cells. Furthermore, mechanism explorations revealed that Wnt/β-catenin signaling transcriptionally regulated the expression of miR-142a-5p during osteogenic differentiation. β-catenin binds to the T-cell factor/lymphoid enhancer factor binding motif within the promoter of miR-142 and positively regulates its transcriptional activity. Our findings suggested that miR-142a-5p promoted osteoblast differentiation via targeting NFIA.

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“…Parathyroid hormone-related protein (PTHrP encoded by PTHLH) is a key regulator of transitional chondrocytes and is secreted by articular chondrocytes and perichondrium cells. PTHrP was reported to maintain the continuous proliferation of chondrocytes and inhibit their terminal differentiation into hypertrophic chondrocytes after mitosis (Pelosi et al 2013;Singh et al 2018). One study has also shown that the partial regulatory effect of ERG on chondrocytes is mediated by PTHrP (Okabe et al 2011).…”

Section: Introductionmentioning

confidence: 99%

The miR-200b-3p/ERG/PTHrP Axis Mediates the Inhibitory Effect of Ethanol on the Differentiation of Rat Fetal Chondrocytes into Articular Cartilage

Chen

et al. 2021

Preprint

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Background This study aims to further explore cartilage development in prenatal ethanol exposure (PEE) offspring at different times to explore the specific time points and mechanism of ethanol-induced fetal cartilage dysplasia. Methods On gestational day (GD)14, GD17, and GD20, PEE fetal cartilage was evaluated by morphological analysis. RT-qPCR, immunohistochemistry, and immunofluorescence were used to detect the expression of cartilage marker genes and their regulatory factors. Bone marrow mesenchymal stem cells (BMSCs) were used to explore the effect of ethanol on the differentiation of chondrocytes. Additionally, we used inhibitors, overexpression plasmids and a luciferase reporter assay on GD17 chondrocytes to verify the mechanism. Findings: PEE significantly reduced cartilage matrix content and the expression of marker genes on GD17 and GD20 but had no effect on GD14. The inhibition of chondrogenic differentiation by PEE mainly occurred on GD14-17. Furthermore, the expression of miR-200b-3p was increased, while that of ERG and PTHrP was markedly reduced in PEE fetal cartilage. In vitro, ethanol (30–120 mM) inhibited the differentiation of BMSCs into chondrocytes in a concentration-dependent manner, accompanied by strong expression of miR-200b-3p and low expression of ERG and PTHrP. Moreover, PTHLH and ERG overexpressed, as well as a miR-200b-3p inhibitor reversed the inhibitory effect of ethanol on the differentiation of fetal chondrocytes. Furthermore, miR-200b-3p could target and negatively regulate ERG. Interpretation: PEE can significantly inhibit the development of articular cartilage, especially during articular cartilage formation. The mechanism is related to the decreased differentiation of fetal cartilage into articular cartilage mediated by the miR-200b-3p/ERG/PTHrP axis.

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NFIA and GATA3 are crucial regulators of embryonic articular cartilage differentiation

Cited by 22 publications

References 45 publications

Lgr5 and Col22a1 Mark Progenitor Cells in the Lineage toward Juvenile Articular Chondrocytes

Lgr5 and Col22a1 Mark Progenitor Cells in the Lineage toward Juvenile Articular Chondrocytes

miR‐142a‐5p promoted osteoblast differentiation via targeting nuclear factor IA

The miR-200b-3p/ERG/PTHrP Axis Mediates the Inhibitory Effect of Ethanol on the Differentiation of Rat Fetal Chondrocytes into Articular Cartilage

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