ArticleArthritis & rheumatology (Hoboken, N.J.)2018
Functional Characterization of the Osteoarthritis Genetic Risk Residing at ALDH1A2 Identifies rs12915901 as a Key Target Variant.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 4 of them syntheses that pooled it.
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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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Who cites it
29 citing papers in PubMed, 4 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Pooled it
- Meta-analysis of erosive hand osteoarthritis identifies four common variants that associate with relatively large effect.Annals of the rheumatic diseases · 2023Pooled it
- Allelic expression imbalance in articular cartilage and subchondral bone refined genome-wide association signals in osteoarthritis.Rheumatology (Oxford, England) · 2023Pooled it
- Identifying Novel Osteoarthritis-Associated Genes in Human Cartilage Using a Systematic Meta-Analysis and a Multi-Source Integrated Network.International journal of molecular sciences · 2022Pooled it
- Transcriptomic analysis reveals distinct molecular signatures and regulatory networks of osteoarthritic chondrocytes versus mesenchymal stem cells during chondrogenesis.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2025Article
- Review
- The methylomic landscape of human articular cartilage development contains epigenetic signatures of osteoarthritis risk.American journal of human genetics · 2024Article
- Comparative Analysis of Osteoarthritis Therapeutics: A Justification for Harnessing Retrospective Strategies via an Inverted Pyramid Model Approach.Biomedicines · 2024Review
- Skeletal growth is enhanced by a shared role for SOX8 and SOX9 in promoting reserve chondrocyte commitment to columnar proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Association of blood vitamin A with osteoarthritis: a nationally representative cross-sectional study.Frontiers in nutrition · 2024Article
- Genetic risk of osteoarthritis operates during human skeletogenesis.Human molecular genetics · 2023Article
- Bone-cartilage crosstalk informed by aging mouse bone transcriptomics and human osteoarthritis genome-wide association studies.Bone reports · 2023Article
- Mediation of the Same Epigenetic and Transcriptional Effect by Independent Osteoarthritis Risk-Conferring Alleles on a Shared Target Gene, COLGALT2.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- A Functional Polymorphism Downstream of Vitamin A Regulator GeneInternational journal of molecular sciences · 2023Article
- Inflammation-Driven Secretion Potential Is Upregulated in Osteoarthritic Fibroblast-Like Synoviocytes.International journal of molecular sciences · 2022Article
- Identification of candidate enhancers controlling the transcriptome during the formation of interphalangeal joints.Scientific reports · 2022Article
- Genetics of osteoarthritis.Osteoarthritis and cartilage · 2022Review
- An eQTL variant of ALDH1A2 is associated with Kashin-Beck disease in Chinese population.Journal of bone and mineral metabolism · 2022Article
- Epigenetic Regulation in Knee Osteoarthritis.Frontiers in genetics · 2022Review
- E-liquids and vanillin flavoring disrupts retinoic acid signaling and causes craniofacial defects in Xenopus embryos.Developmental biology · 2022Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveTo identify the functional single-nucleotide polymorphisms (SNPs) and mechanisms conferring increased risk of hand osteoarthritis (OA) at the ALDH1A2 locus, which is a retinoic acid regulatory gene.
methodsTissue samples from 247 patients with knee, hip, or hand OA who had undergone joint surgery were included. RNA-sequencing analysis was used to investigate differential expression of ALDH1A2 and other retinoic acid signaling pathway genes in cartilage. Expression of ALDH1A2 in joint tissues obtained from multiple sites was quantified using quantitative reverse transcription-polymerase chain reaction. Allelic expression imbalance (AEI) was measured by pyrosequencing. The consequences of ALDH1A2 depletion by RNA interference were assessed in primary human chondrocytes. In silico and in vitro analyses were used to pinpoint which, among 62 highly correlated SNPs, could account for the association at the locus.
resultsALDH1A2 expression was observed across multiple joint tissue samples, including osteochondral tissue from the hand. The expression of ALDH1A2 and of several retinoic acid signaling genes was different in diseased cartilage compared to non-diseased cartilage, with ALDH1A2 showing lower levels in OA cartilage. Experimental depletion of ALDH1A2 resulted in changes in the expression levels of a number of chondrogenic markers, including SOX9. In addition, reduced expression of the OA risk-conferring allele was witnessed in a number of joint tissues, with the strongest effect in cartilage. The intronic SNP rs12915901 recapitulated the AEI observed in patient tissues, while the Ets transcription factors were identified as potential mediators of this effect.
conclusionThe ALDH1A2 locus seems to increase the risk of hand OA through decreased expression of ALDH1A2 in joint tissues, with the effect dependent on rs12915901. These findings indicate a mechanism that may now be targeted to modulate OA risk.
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