ArticleScientific reports2020
Transglutaminase-2 regulates Wnt and FoxO3a signaling to determine the severity of osteoarthritis.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- Energy crisis and cartilage collapse: metabolic reprogramming of chondrocytes in osteoarthritis.Frontiers in immunology · 2026Review
- Potential glutamine metabolism-related biomarkers were identified in osteoarthritis by bioinformatics.Scientific reports · 2025Article
- Research progress and prospect of MAPK signaling pathway in knee osteoarthritis.European journal of orthopaedic surgery & traumatology : orthopedie traumatologie · 2025Review
- Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.Journal for immunotherapy of cancer · 2025Article
- The role of FoxO3a in the pathogenesis of osteoarthritis and its therapeutic applications.Frontiers in immunology · 2025Review
- The Roles of Forkhead Box O3a (FOXO3a) in Bone and Cartilage Diseases - A Narrative Review.Drug design, development and therapy · 2025Review
- GPR56 signaling pathway network and its dynamics in the mesenchymal transition of glioblastoma.Journal of cell communication and signaling · 2023Article
- TGM2 accelerates migration and differentiation of BMSCs by activating Wnt/β-catenin signaling.Journal of orthopaedic surgery and research · 2023Article
- Type 2 transglutaminase in the nucleus: the new epigenetic face of a cytoplasmic enzyme.Cellular and molecular life sciences : CMLS · 2023Review
- miR-122 and the WNT/β-catenin pathway inhibit effects of both interleukin-1β and tumor necrosis factor-α in articular chondrocytes in vitro.Journal of cellular biochemistry · 2022Article
- Enzymatic Machinery of Ubiquitin and Ubiquitin-Like Modification Systems in Chondrocyte Homeostasis and Osteoarthritis.Current rheumatology reports · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transglutaminase 2 (TG2), also known as tissue transglutaminase, is a calcium-dependent enzyme that has a variety of intracellular and extracellular substrates. TG2 not only increases in osteoarthritis (OA) tissue but also affects the progression of OA. However, it is still unclear how TG2 affects cartilage degradation in OA at the molecular level. Surgically induced OA lead to an increase of TG2 in the articular cartilage and growth plate, and it was dependent on TGFβ1 in primary chondrocytes. The inhibition of TG2 enzymatic activity with intra-articular injection of ZDON, the peptide-based specific TG2 inhibitor, ameliorated the severity of surgically induced OA as well as the expression of MMP-3 and MMP-13. ZDON attenuated MMP-3 and MMP-13 expression in TGFβ- and calcium ionophore-treated chondrocytes in a Runx2-independent manner. TG2 inhibition with ZDON suppressed canonical Wnt signaling through a reduction of β-catenin, which was mediated by ubiquitination-dependent proteasomal degradation. In addition, TG2 activation by a calcium ionophore enhanced the phosphorylation of AMPK and FoxO3a and the nuclear translocation of FoxO3a, which was responsible for the increase in MMP-13. In conclusion, TG2 plays an important role in the pathogenesis of OA as a major catabolic mediator that affects the stability of β-catenin and FoxO3a-mediated MMP-13 production.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.