ArticleArthritis and rheumatism2012
Smad3 controls β-1,3-glucuronosyltransferase 1 expression in rat nucleus pulposus cells: implications of dysregulated expression in disc disease.
Article in Arthritis and rheumatism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Advancing Intervertebral Disc Biology via Omics: Implications for Nucleus Pulposus Progenitor Cell-Based Regeneration.JOR spine · 2025Review
- Role of macrophage in intervertebral disc degeneration.Bone research · 2025Review
- Investigating the regulation of the miR-199a-3p/TGF-β/Smad signaling pathway by BSHXF drug-containing serum combined with ADSCs for delaying intervertebral disc degeneration.Frontiers in pharmacology · 2025Article
- Assessment of the Concentration of Transforming Growth Factor Beta 1-3 in Degenerated Intervertebral Discs of the Lumbosacral Region of the Spine.Current issues in molecular biology · 2024Article
- Review
- Article
- Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- TGF-β1 suppresses syndecan-2 expression through the ERK signaling pathway in nucleus pulposus cells.International journal of clinical and experimental pathology · 2018Article
- Mechanosignaling activation of TGFβ maintains intervertebral disc homeostasis.Bone research · 2017Article
- TGFβ regulates Galectin-3 expression through canonical Smad3 signaling pathway in nucleus pulposus cells: implications in intervertebral disc degeneration.Matrix biology : journal of the International Society for Matrix Biology · 2016Article
- 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
- Origin of M2 Mϕ and its macrophage polarization by TGF-β in a mice intervertebral injury model.International journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveTo study the regulation of expression of β-1,3-glucuronosyltransferase 1 (GlcAT-1), an important regulator of glycosaminoglycan (GAG) synthesis, by Smad3 in nucleus pulposus (NP) cells.
methodsGlcAT-1 expression was examined in rat NP and anulus fibrosus (AF) cells treated with transforming growth factor β (TGFβ). The effects of Smad signaling and Smad suppression on GlcAT-1 were examined in rat NP cells. GlcAT-1 expression was analyzed in the discs of Smad3-null mice and in degenerated human NP tissue.
resultsTGFβ increased the expression of GlcAT-1 in rat NP but not rat AF cells. Suppression of GlcAT-1 promoter activity was evident with dominant-negative ALK-5 (DN-ALK-5). Cotransfection with Smad3 strongly induced promoter activity independent of TGFβ. Bioinformatics analysis indicated the presence of several Smad binding sites in the promoter; deletion analysis showed that the region between -274 and -123 bp was required for Smad3 response. DN-Smad3, Smad 3 small interfering RNA, and Smad7 strongly suppressed basal as well as TGFβ-induced promoter activity. Induction of promoter activity by Smad3 was significantly blocked by DN-Smad3; Smad7 had a very small effect. Lentiviral transduction of NP cells with short hairpin RNA Smad3 resulted in a decrease in GlcAT-1 expression and accumulation of GAG. Compared to wild-type mice, significantly lower expression of GlcAT-1 was seen in the discs of Smad3-null mice. Analysis of degenerated human NP tissue specimens showed no positive correlation between GlcAT-1 and TGFβ expression. Moreover, isolated cells from degenerated human tissue showed a lack of induction of GlcAT-1 expression following TGFβ treatment, suggesting an altered response.
conclusionOur findings demonstrate that in healthy NP cells, the TGFβ-Smad3 axis serves as a regulator of GlcAT-1 expression. However, an altered responsiveness to TGFβ during disc degeneration may compromise GAG synthesis.
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