ArticleAnnals of the rheumatic diseases2015
Underlying molecular mechanisms of DIO2 susceptibility in symptomatic osteoarthritis.
Article in Annals of the rheumatic diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 93 citations in OpenAlex.
- Reversing detrimental effects of OA-related terminal maturation in high-throughput in vitro and biomimetic ex vivo human models.Arthritis research & therapy · 2026Article
- Evaluating therapeutic efficacy of iopanoic acid in a DMM-induced osteoarthritis mouse model and osteochondral lesioned human explants.Osteoarthritis and cartilage open · 2026Article
- Endocrine‑metabolic imbalance drives osteoarthritis: From whole‑joint pathobiology to precision therapy (Review).International journal of molecular medicine · 2026Review
- Article
- Characterizing the Long Non-Coding RNA Profile of Endometrial Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Anti-Inflammatory Role in Osteoarthritis.International journal of molecular sciences · 2025Article
- Insight into the shared pathogenic link between COVID-19 and pterygium: a systematic bioinformatics analysis with experimental validation.Hereditas · 2025Article
- DNA methylation and its influence on the pathogenesis of osteoarthritis: a systematic literature review.EFORT open reviews · 2025Article
- Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk.Cell genomics · 2025Article
- Transcriptomic Changes During the Replicative Senescence of Human Articular Chondrocytes.International journal of molecular sciences · 2024Article
- Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk.bioRxiv : the preprint server for biology · 2024Article
- Association of thyroid hormone with osteoarthritis: from mendelian randomization and RNA sequencing analysis.Journal of orthopaedic surgery and research · 2024Article
- Thyroid hormone induces ossification and terminal maturation in a preserved OA cartilage biomimetic model.Arthritis research & therapy · 2024Article
- Genetic predisposition to thyrotoxicosis and onset of knee osteoarthritis.Frontiers in endocrinology · 2024Article
- Selenium and Selenoproteins in Health.Biomolecules · 2023Review
- Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers.Scientific reports · 2023Article
- Identification and functional characterization of imbalanced osteoarthritis-associated fibronectin splice variants.Rheumatology (Oxford, England) · 2023Article
- The epigenetic players and the chromatin marks involved in the articular cartilage during osteoarthritis.Frontiers in physiology · 2023Review
- Detection of selenoprotein transcriptome in chondrocytes of patients with Kashin-Beck disease.Frontiers in cell and developmental biology · 2023Article
- Mutation in the CCAL1 locus accounts for bidirectional process of human subchondral bone turnover and cartilage mineralization.Rheumatology (Oxford, England) · 2022Article
- Inhibiting thyroid activation in aged human explants prevents mechanical induced detrimental signalling by mitigating metabolic processes.Rheumatology (Oxford, England) · 2022Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo investigate how the genetic susceptibility gene DIO2 confers risk to osteoarthritis (OA) onset in humans and to explore whether counteracting the deleterious effect could contribute to novel therapeutic approaches.
methodsEpigenetically regulated expression of DIO2 was explored by assessing methylation of positional CpG-dinucleotides and the respective DIO2 expression in OA-affected and macroscopically preserved articular cartilage from end-stage OA patients. In a human in vitro chondrogenesis model, we measured the effects when thyroid signalling during culturing was either enhanced (excess T3 or lentiviral induced DIO2 overexpression) or decreased (iopanoic acid).
resultsOA-related changes in methylation at a specific CpG dinucleotide upstream of DIO2 caused significant upregulation of its expression (β=4.96; p=0.0016). This effect was enhanced and appeared driven specifically by DIO2 rs225014 risk allele carriers (β=5.58, p=0.0006). During in vitro chondrogenesis, DIO2 overexpression resulted in a significant reduced capacity of chondrocytes to deposit extracellular matrix (ECM) components, concurrent with significant induction of ECM degrading enzymes (ADAMTS5, MMP13) and markers of mineralisation (ALPL, COL1A1). Given their concurrent and significant upregulation of expression, this process is likely mediated via HIF-2α/RUNX2 signalling. In contrast, we showed that inhibiting deiodinases during in vitro chondrogenesis contributed to prolonged cartilage homeostasis as reflected by significant increased deposition of ECM components and attenuated upregulation of matrix degrading enzymes.
conclusionsOur findings show how genetic variation at DIO2 could confer risk to OA and raised the possibility that counteracting thyroid signalling may be a novel therapeutic approach.
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