ArticleScientific reports2017
Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases.Journal of orthopaedic translation · 2025Review
- Exploring adenosine analogs for chondrosarcoma therapy:Molecular therapy. Nucleic acids · 2025Article
- Targeting one-carbon metabolism for cancer immunotherapy.Clinical and translational medicine · 2024Review
- Predicting target-ligand interactions with graph convolutional networks for interpretable pharmaceutical discovery.Scientific reports · 2022Article
- The benefit of combining curcumin, bromelain and harpagophytum to reduce inflammation in osteoarthritic synovial cells.BMC complementary medicine and therapies · 2021Article
- EZH2 is associated with cartilage degeneration in osteoarthritis by promoting SDC1 expression via histone methylation of the microRNA-138 promoter.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Reduction of Matrix Metallopeptidase 13 and Promotion of Chondrogenesis by Zeel T in Primary Human Osteoarthritic Chondrocytes.Frontiers in pharmacology · 2021Article
- Histone Modifications and Chondrocyte Fate: Regulation and Therapeutic Implications.Frontiers in cell and developmental biology · 2021Review
- EZH2 inhibition reduces cartilage loss and functional impairment related to osteoarthritis.Scientific reports · 2020Article
- Histone Methylation: Achilles Heel and Powerful Mediator of Periodontal Homeostasis.Journal of dental research · 2020Article
- Development of a simple osteoarthritis model useful to predict in vitro the anti-hypertrophic action of drugs.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- [Correlation between histone methylation level and pathological development of osteoarthritis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2019Review
- Inhibition of EZH2 ameliorates cartilage endplate degeneration and attenuates the progression of intervertebral disc degeneration via demethylation of Sox-9.EBioMedicine · 2019Article
- Osteoarthritis year in review 2018: genetics and epigenetics.Osteoarthritis and cartilage · 2019Review
- KDM6A promotes chondrogenic differentiation of periodontal ligament stem cells by demethylation of SOX9.Cell proliferation · 2018Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
3-Deazaneplanocin A (DZNep) is an inhibitor of S-Adenosyl-L-Homocysteine Hydrolase (SAHH) known to inhibit EZH2, a histone methylase upregulated during osteoarthritis. In this study, we assessed its effects in human articular chondrocytes. Anti-inflammatory effects were assessed by Nitric Oxide (NO), Prostaglandin E2 (PGE2) and Metalloprotease (MMP) release in IL-1β-stimulated chondrocytes. MAPK and NFκB activation was analyzed by western blotting. Differentially expressed genes (DEG) regulated by DZNep were identified by whole-transcriptome microarray. DZNep inhibited SAHH activity and was not toxic. It counteracted NO, PGE2 and MMP release, and reduced MAPK activation induced by IL-1β. By whole-transcriptome analysis, we identified that DNZep counteracts the effect of IL-1β on the expression of 81 protein-coding genes, including CITED2, an MMP inhibitor. These genes are organized in a protein-protein network centred on EGR1, which is known to functionally interact with EZH2. Gene ontologies enrichment analysis confirmed that DZNep counteracts IL-1β-induced expression of genes involved in cartilage matrix breakdown (MMPs and ADAMTS). In addition, DZNep up-regulated cartilage specific genes, such as COL2A1 and SOX9, suggesting a chondroprotective effect of DZNep. DZNep exhibits anti-inflammatory effects, and regulates genes implicated in chondroprotective response in human articular chondrocytes, suggesting that inhibitors of S-adenosylmethionine-dependent methyltransferases could be effective treatments for OA.
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