Identification of cis and trans-acting transcriptional regulators in chondroinduced fibroblasts from the pre-phenotypic gene expression profile

Yates, Karen E.

doi:10.1016/j.gene.2006.03.005

Cited by 13 publications

(14 citation statements)

References 35 publications

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“…Furthermore, a recent study which examined the process of chondrogenic differentiation induced in human dermal fibroblasts cultured in collagen sponges containing demineralized bone powder found a remarkable increase in SOX9 gene expression which was accompanied by a two fold increase in CREB protein, and a three-fold in CREB phosphorylation [47] In other studies, CREB has been implicated in PTHrP signaling pathway in chondrocytes [48]. In these studies it was demonstrated that inhibition of CREB function during PTHrP signaling led to a decrease in chondrocyte proliferation and an increase in maturation, similar to that observed in PTHrP-KO mice [49].…”

Section: Discussionmentioning

confidence: 99%

Regulation of the human SOX9 promoter by Sp1 and CREB

Piera-Velázquez

Hawkins

Whitecavage

et al. 2007

Experimental Cell Research

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The transcription factor SOX9 is essential for multiple steps during skeletal development, including mesenchymal cell chondrogenesis and endochondral bone formation. We recently reported that the human SOX9 proximal promoter region is regulated by the CCAAT-binding factor through two CCAAT boxes located within 100 bp of the transcriptional start site. Here we report that the human SOX9 proximal promoter is also regulated by the cyclic-AMP response element binding protein (CREB) and Sp1. We show by DNaseI protection and EMSA analysis that CREB and Sp1 interact with specific sites within the SOX9 proximal promoter region. By transient transfection analysis we also demonstrate that mutations of the CREB and Sp1 binding sites result in a profound reduction of SOX9 promoter activity. Chromatin immunoprecipitation (ChIP) assay demonstrated that both Sp1 and CREB interact with the SOX9 promoter in vivo. Finally, we demonstrate that IL-1β treatment of chondrocytes isolated from human normal and osteoarthritic (OA) cartilage down-regulates SOX9 promoter activity, an effect accompanied by a reduction of Sp1 binding to the SOX9 proximal promoter.

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Section: Discussionmentioning

confidence: 99%

Regulation of the human SOX9 promoter by Sp1 and CREB

Piera-Velázquez

Hawkins

Whitecavage

et al. 2007

Experimental Cell Research

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“…Kubo et al also reported that cell differentiation and juvenile properties are affected when ETV1 is knocked down using short interfering RNA; for example, the self-renewal capacity of MSCs was repressed. Another study reported that the expression of STAT4, which is regulated by miR-320c, was upregulated in cells in which chondrocyte differentiation has been induced compared with a control group, 25 suggesting that STAT4 affects cartilage differentiation.…”

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confidence: 99%

MicroRNA‐199a‐3p, microRNA‐193b, and microRNA‐320c are correlated to aging and regulate human cartilage metabolism

Ukai

Sato

Akutsu

et al. 2012

Journal Orthopaedic Research

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MicroRNAs (miRNAs) are small RNAs of $22 base pairs that regulate gene expression. We harvested cartilage tissue from patients with polydactylism, anterior cruciate ligament injury, and osteoarthritis undergoing total knee arthroplasty and used microarrays to identify miRNAs whose expression is upregulated or downregulated with age. The results were assessed by real-time PCR and MTT assay in a mimic group, in which synthetic double-stranded RNA from the isolated miRNA was transfected to upregulate expression, and in an inhibitor group, in which the miRNA was bound specifically to downregulate expression. The expression of two miRNAs (miR-199a-3p and miR-193b) was upregulated with age and that of one miRNA (miR-320c) was downregulated with age. A real-time PCR assay showed that type 2 collagen, aggrecan, and SOX9 expression were downregulated in the miR-199a-3p mimic group but was upregulated in the inhibitor group. Similar results were observed for miR-193b. By contrast, ADAMTS5 expression was downregulated in the miR-320c mimic group and upregulated in the inhibitor group. Cell proliferative activity was upregulated significantly in the miR-193b inhibitor group compared with the control group. We believe that miR-199a-3p and miR-193b are involved in the senescence of chondrocytes, and miR-320c is involved in the juvenile properties of chondrocytes. ß

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“…TGFBIp, a product of TGFb1 treatment, has an Arg-Gly-Asp (RGD) motif and interacts with several extracellular matrix proteins, including collagens (Hashimoto et al 1997;Runager et al 2008). It is up-regulated during the differentiation of chondrocytes, from the early stage of chondrogenic differentiation of mesenchymal stem cells (Ohno et al 2002;Yates 2006) to the terminal differentiation of chondrocytes during endochondral ossification (Han et al 2008). Immunohistochemistry revealed that TGFBIp is located pericellularly but its distribution is beyond the PCM defined by type VI collagen staining.…”

Section: Discussionmentioning

confidence: 99%

A proteomic approach for identification and localization of the pericellular components of chondrocytes

Zhang

Beckett

et al. 2011

Histochem Cell Biol

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Although the pericellular matrix (PCM) plays a central role in the communication between chondrocytes and extracellular matrix, its composition is largely unknown. In this study, the PCM was investigated with a proteomic approach using chondrons, which are enzymatically isolated constructs including the chondrocyte and its surrounding PCM. Chondrons and chondrocytes alone were isolated from human articular cartilage. Proteins extracted from chondrons and chondrocytes were used for two-dimensional electrophoresis. Protein spots were quantitatively compared between chondron and chondrocyte gels. Cellular proteins, which had similar density between chondron and chondrocyte gels, did not proceed for analysis. Since chondrons only differ from chondrocytes in association of the PCM, protein spots in the chondron gels that had higher quantity than that in the chondrocyte gels were selected as candidates of the PCM components and processed for mass spectrometry. Among 15 identified peptides, several were fragments of the three type VI collagen chains (α-1, α-2, and α-3). Other identified PCM proteins included triosephosphate isomerase, transforming growth factor-β induced protein, peroxiredoxin-4, ADAM (A disintegrin and metalloproteinases) 28, and latent-transforming growth factor beta-binding protein-2. These PCM components were verified with immunohisto(cyto)chemistry for localization in the PCM region of articular cartilage. The abundance of type VI collagen in the PCM emphasizes its importance to the microenvironment of chondrocytes. Several proteins were localized in the PCM of chondrocytes for the first time and that warrants further investigation for their functions in cartilage biology.

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Identification of cis and trans-acting transcriptional regulators in chondroinduced fibroblasts from the pre-phenotypic gene expression profile

Cited by 13 publications

References 35 publications

Regulation of the human SOX9 promoter by Sp1 and CREB

Regulation of the human SOX9 promoter by Sp1 and CREB

MicroRNA‐199a‐3p, microRNA‐193b, and microRNA‐320c are correlated to aging and regulate human cartilage metabolism

A proteomic approach for identification and localization of the pericellular components of chondrocytes

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