Characterization and chondrocyte differentiation stage-specific expression of KRAB zinc-finger protein gene ZNF470

Hering, Thomas M.; Kazmi, Najam; Huynh, Tru D.; Kollar, John; Xu, Laura Xiao Xia; Hunyady, Aaron B; Johnstone, Brian

doi:10.1016/j.yexcr.2004.05.030

Cited by 14 publications

(9 citation statements)

References 67 publications

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“…The samples used for this analysis were from a different human MSC differentiation experiment that examined chondrogenesis from days 0 to 14, and was previously analyzed for total COL2A1 expression (Hering et al, 2004). In this experiment, COL2A1 expression over time Table 1 PCR primers and hybridization probes for amplification and identification of alternatively spliced COL2A1cDNA fragments Oligo Sequence…”

Section: Cloning and Sequencing The Human Iic Isoformmentioning

confidence: 99%

Expression of two novel alternatively spliced COL2A1 isoforms during chondrocyte differentiation

et al. 2008

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Alternative splicing of the type II procollagen gene (COL2A1) is developmentally regulated during chondrogenesis. Type IIA procollagen (+ exon 2) is synthesized by chondroprogenitor cells while type IIB procollagen (- exon 2) is synthesized by differentiated chondrocytes. Here, we report expression of two additional alternatively spliced COL2A1 isoforms during chondrocyte differentiation of bone marrow-derived mesenchymal stem cells (MSCs). One isoform, named IIC, contains only the first 34 nucleotides of exon 2 by the use of an alternative 5' splice site, resulting in a premature termination codon and possible nonsense-mediated decay of IIC mRNA. Low levels of the IIC isoform were detected by RT-PCR and Southern analysis of COL2A1 cDNA amplified from differentiating rabbit and human MSCs. A second novel transcript, named IID, arises by the use of another 5' alternative splice site in intron 2. The IID isoform contains exon 2 plus 3 nucleotides, resulting in the insertion of an additional amino acid. The IID isoform was co-expressed with the IIA isoform during chondrogenesis, and was approximately one-third as abundant. Deletion of the IIC alternative 5' splice site from a COL2A1 mini-gene construct resulted in a significant increase in the IIA:IIB ratio. A mutant mini-gene that inhibited production of the IID isoform, however, had differential effects on the production of the IIA and IIB isoforms: this was apparently related to the differentiation status of the cell type used. These data suggest that COL2A1 mRNA abundance and other aspects of chondrocyte differentiation may be regulated by the use of these previously undetermined alternative splice sites.

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Section: Cloning and Sequencing The Human Iic Isoformmentioning

confidence: 99%

Expression of two novel alternatively spliced COL2A1 isoforms during chondrocyte differentiation

et al. 2008

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“…Basic FGF produces neurogenic, proliferative, and patterning effects on adult CNS stem cells (Dono, 2003;Cayuso and Marti, 2005). RA is a commonly used neural induction reagent in vitro (McCaffery et al, 2003;Mey and McCaffery, 2004) and enhances expression of markers of neural crest and stimulates de-differentiation of articular chondrocytes (Hering et al, 2004). However, it is unlikely that bmercaptoethanol and DMSO (final concentration: 0.1%, used as the dissolve reagent for b-mercaptoethanol 1,000Â stock) present in the culture medium played any role in the conversion in our preparation as the concentrations used were too low to cause the reported artifact (Lu et al, 2004;Neuhuber et al, 2004;Bertani et al, 2005), and the omission of these chemicals reproduced the same results.…”

Section: Mechanisms Underlying the Conversion From Chondrocytes To Nementioning

confidence: 99%

Potential conversion of adult clavicle‐derived chondrocytes into neural lineage cells in vitro

Zhou

2007

Journal Cellular Physiology

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Neural stem cells (NSC) can be isolated from a variety of adult tissues and become a valuable cell source for the repair of peripheral and central nervous diseases. However, their origin and identity remain controversial because of possible de-differentiation/trans-differentiation or contaminations by hematopoietic stem cells (HSCs) or mesenchymal stem cells (MSCs). We hypothesize that the commonly used NSC culture medium can induce committed cartilage chondrocytes to de-differentiate and/or trans-differentiate into neural cell lineages. Using a biological isolation and purification method with explants culture, we here show that adult rat clavicle cartilage chondrocytes migrate out from tissue blocks, form sphere-like structures, possess the capability of self-renewal, express nestin and p75NTR, markers for neural crest progenitors, and differentiate into neurons, glia, and smooth muscle cells. Comparing with adult cartilage, the spherical-forming neural crest cell-like cells downregulate the chondrocytic marker genes, including collagen II, collagen X, and sox9, as well as neural-lineage repressors/silencers REST and coREST, but upregulate a set of well-defined genes related to neural crest cells and pro-neural potential. Nerve growth factor (NGF) and glial growth factor (GGF) increase glial and neuronal differentiation, respectively. These results suggest that chondrocytes derived from adult clavicle cartilage can become neural crest stem-like cells and acquire neuronal phenotypes in vitro. The possible de-differentiation/trans-differentiation mechanisms underlying the conversion were discussed.

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“…ZNF470 is a protein with 17 zinc fingers as well as KRAB-A and KRAB-B motifs, whose mRNA was originally isolated from mesenchymal progenitors induced to differentiate towards chondrocytes in vitro. The ZNF470 transcript was found transiently expressed during chondrogenesis, with a peak of maximal abundance that coincided with the beginning of the increase in COL2A1 expression, and was strongly upregulated during the dedifferentiation of bovine articular chondrocytes in response to retinoic acid treatment [31]. …”

Section: Introductionmentioning

confidence: 99%

Expression Profiling and Functional Implications of a Set of Zinc Finger Proteins, ZNF423, ZNF470, ZNF521, and ZNF780B, in Primary Osteoarthritic Articular Chondrocytes

Mesuraca

Galasso

Guido

et al. 2014

Mediators of Inflammation

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Articular chondrocytes are responsible for the maintenance of healthy articulations; indeed, dysregulation of their functions, including the production of matrix proteins and matrix-remodeling proteases, may result in fraying of the tissue and development of osteoarthritis (OA). To explore transcriptional mechanisms that contribute to the regulation of chondrocyte homeostasis and may be implicated in OA development, we compared the gene expression profile of a set of zinc finger proteins potentially linked to the control of chondrocyte differentiation and/or functions (ZNF423, ZNF470, ZNF521, and ZNF780B) in chondrocytes from patients affected by OA and from subjects not affected by OA. This analysis highlighted a significantly lower expression of the transcript encoding ZNF423 in chondrocytes from OA, particularly in elderly patients. Interestingly, this decrease was mirrored by the similarly reduced expression of PPARγ, a known target of ZNF423 with anti-inflammatory and chondroprotective properties. The ZNF521 mRNA instead was abundant in all primary chondrocytes studied; the RNAi-mediated silencing of this gene significantly altered the COL2A/COL1 expression ratio, associated with the maintenance of the differentiated phenotype, in chondrocytes cultivated in alginate beads. These results suggest a role for ZNF423 and ZNF521 in the regulation of chondrocyte homeostasis and warrant further investigations to elucidate their mechanism of action.

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Characterization and chondrocyte differentiation stage-specific expression of KRAB zinc-finger protein gene ZNF470

Cited by 14 publications

References 67 publications

Expression of two novel alternatively spliced COL2A1 isoforms during chondrocyte differentiation

Expression of two novel alternatively spliced COL2A1 isoforms during chondrocyte differentiation

Potential conversion of adult clavicle‐derived chondrocytes into neural lineage cells in vitro

Expression Profiling and Functional Implications of a Set of Zinc Finger Proteins, ZNF423, ZNF470, ZNF521, and ZNF780B, in Primary Osteoarthritic Articular Chondrocytes

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