ArticleHuman molecular genetics2018
A hyperactivating proinflammatory RIPK2 allele associated with early-onset osteoarthritis.
Article in Human molecular genetics, 2018. 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 12 papers.
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Who cites it
12 citing papers in PubMed, 31 citations in OpenAlex.
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- Receptor interacting serine/threonine kinase 2 promotes rheumatoid arthritis progression and partially regulates nuclear factor kappa B pathway.CytoJournal · 2024Article
- Nod1-dependent NF-kB activation initiates hematopoietic stem cell specification in response to small Rho GTPases.Nature communications · 2023Article
- Recent advances in the development of RIPK2 modulators for the treatment of inflammatory diseases.Frontiers in pharmacology · 2023Review
- A novel uveitis model induced by lipopolysaccharide in zebrafish.Frontiers in immunology · 2022Article
- Comparative and evolutionary analysis ofFrontiers in genetics · 2022Article
- Acromial and glenoid morphology in glenohumeral osteoarthritis: a three-dimensional analysis.JSES international · 2021Article
- Familial Clustering of Erosive Hand Osteoarthritis in a Large Statewide Cohort.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- Evaluation for Kienböck Disease Familial Clustering: A Population-Based Cohort Study.The Journal of hand surgery · 2020Article
- Multi-pathway Protective Effects of MicroRNAs on Human Chondrocytes in an In Vitro Model of Osteoarthritis.Molecular therapy. Nucleic acids · 2019Article
- Zebrafish Models of Human Skeletal Disorders: Embryo and Adult Swimming Together.BioMed research international · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Osteoarthritis (OA) is a common debilitating disease characterized by abnormal remodeling of the cartilage and bone of the articular joint. Ameliorating therapeutics are lacking due to limited understanding of the molecular pathways affecting disease initiation and progression. Notably, although a link between inflammation and overt OA is well established, the role of inflammation as a driver of disease occurrence is highly disputed. We analyzed a family with dominant inheritance of early-onset OA and found that affected individuals harbored a rare variant allele encoding a significant amino acid change (p.Asn104Asp) in the kinase domain of receptor interacting protein kinase 2 (RIPK2), which transduces signals from activated bacterial peptidoglycan sensors through the NF-κB pathway to generate a proinflammatory immune response. Functional analyses of RIPK2 activity in zebrafish embryos indicated that the variant RIPK2104Asp protein is hyperactive in its signaling capacity, with augmented ability to activate the innate immune response and the NF-κB pathway and to promote upregulation of OA-associated genes. Further we show a second allele of RIPK2 linked to an inflammatory disease associated with arthritis also has enhanced activity stimulating the NF-κB pathway. Our studies reveal for the first time the inflammatory response can function as a gatekeeper risk factor for OA.
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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.