ArticleArthritis and rheumatism2011
Transforming growth factor β controls CCN3 expression in nucleus pulposus cells of the intervertebral disc.
Article in Arthritis and rheumatism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- The advance of CCN3 in fibrosis.Journal of cell communication and signaling · 2023Review
- Molecular and Genetic Interactions between CCN2 and CCN3 behind Their Yin-Yang Collaboration.International journal of molecular sciences · 2022Review
- Cellular communication network factor 3 in cartilage development and maintenance.Journal of cell communication and signaling · 2021Review
- Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis.International journal of molecular sciences · 2021Review
- Circular RNA derived from TIMP2 functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR‑185‑5p and matrix metalloproteinase 2.International journal of molecular medicine · 2020Article
- The circular RNA FAM169A functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR-583 and BTRC.Cell death & disease · 2020Article
- CircularRNA_104670 plays a critical role in intervertebral disc degeneration by functioning as a ceRNA.Experimental & molecular medicine · 2018Article
- Downregulation of microRNA-193a-3p is involved in invertebral disc degeneration by targeting MMP14.Journal of molecular medicine (Berlin, Germany) · 2016Article
- Effects of CCN3 on rat cartilage endplate chondrocytes cultured under serum deprivation in vitro.Molecular medicine reports · 2016Article
- CCN: core regulatory proteins in the microenvironment that affect the metastasis of hepatocellular carcinoma?Oncotarget · 2016Review
- CCN2 suppresses catabolic effects of interleukin-1β through α5β1 and αVβ3 integrins in nucleus pulposus cells: implications in intervertebral disc degeneration.The Journal of biological chemistry · 2014Article
- ALK5 inhibition blocks TGFβ-induced CCN1 expression in human foreskin fibroblasts.Journal of cell communication and signaling · 2014Article
- Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.Matrix biology : journal of the International Society for Matrix Biology · 2013Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveTo investigate transforming growth factor β (TGFβ) regulation of CCN3 expression in cells of the nucleus pulposus.
methodsReal-time reverse transcription-polymerase chain reaction and Western blot analyses were used to measure CCN3 expression in the nucleus pulposus. Transfections were used to measure the effect of Smad3, MAPKs, and activator protein 1 (AP-1) on TGFβ-mediated CCN3 promoter activity. Lentiviral knockdown of Smad3 was performed to assess the role of Smad3 in CCN3 expression.
resultsCCN3 was expressed in embryonic and adult intervertebral discs. TGFβ decreased the expression of CCN3 and suppressed its promoter activity in nucleus pulposus cells. DN-Smad3, Smad3 small interfering RNA, or DN-AP-1 had little effect on TGFβ suppression of CCN3 promoter activity. However, p38 and ERK inhibitors blocked suppression of CCN3 by TGFβ, suggesting involvement of these signaling pathways in the regulation of CCN3. Interestingly, overexpression of Smad3 in the absence of TGFβ increased CCN3 promoter activity. We validated the role of Smad3 in controlling CCN3 expression in Smad3-null mice and in nucleus pulposus cells transduced with lentiviral short hairpin Smad3. In terms of function, treatment with recombinant CCN3 showed a dose-dependent decrease in the proliferation of nucleus pulposus cells. Moreover, CCN3-treated cells showed a decrease in aggrecan, versican, CCN2, and type I collagen expression.
conclusionThe opposing effect of TGFβ on CCN2 and CCN3 expression and the suppression of CCN2 by CCN3 in nucleus pulposus cells further the paradigm that these CCN proteins form an interacting triad, which is possibly important in maintaining extracellular matrix homeostasis and cell numbers.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.