ArticleAnnals of the rheumatic diseases2023
Human-specific duplicate CHRFAM7A gene is associated with more severe osteoarthritis and amplifies pain behaviours.
Article in Annals of the rheumatic diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- The complexity of pain in osteoarthritis.Nature reviews. Rheumatology · 2026Review
- Sono-piezoelectric cues regulate neuroinflammatory reflex-arc-mediated α7nAChR-P2RX7 axis to dampen osteoarthritis-correlated pain with osteoarthritis attenuation.Theranostics · 2026Article
- The relationship between circulating and tissue biomarkers and OA-related pain: A systematic literature review.Osteoarthritis and cartilage open · 2025Review
- Ion channels as therapeutic targets in osteoarthritis.Trends in pharmacological sciences · 2025Review
- Osteoarthritis.Nature reviews. Disease primers · 2025Review
- The Role of Alpha-7 Nicotinic Acetylcholine Receptors in Pain: Potential Therapeutic Implications.Current neuropharmacology · 2025Review
- Memantine attenuates the development of osteoarthritis by blocking NMDA receptor mediated calcium overload and chondrocyte senescence.Journal of orthopaedic translation · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- CHRFAM7A diversifies human immune adaption through CaEBioMedicine · 2024Article
- Translational implications of CHRFAM7A, an elusive human-restricted fusion gene.Molecular psychiatry · 2024Review
- Songorine modulates macrophage polarization and metabolic reprogramming to alleviate inflammation in osteoarthritis.Frontiers in immunology · 2024Article
- Predicting 'pain genes': multi-modal data integration using probabilistic classifiers and interaction networks.Bioinformatics advances · 2024Article
- Cholinergic Polarization of Human Macrophages.International journal of molecular sciences · 2023Review
- α7- and α9-Containing Nicotinic Acetylcholine Receptors in the Functioning of Immune System and in Pain.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesCHRFAM7A is a uniquely human fusion gene that functions as a dominant negative regulator of alpha 7 acetylcholine nicotinic receptor (α7nAChR) in vitro. This study determined the impact of CHRFAM7A on α7nAChR agonist responses, osteoarthritis (OA) severity and pain behaviours and investigated mechanisms.
methodsTransgenic CHRFAM7A (TgCHRFAM7A) mice were used to determine the impact of CHRFAM7A on knee OA histology, pain severity in OA and other pain models, response to nAchR agonist and IL-1β. Mouse and human cells were used for mechanistic studies.
resultsTransgenic (Tg) TgCHRFAM7A mice developed more severe structural damage and increased mechanical allodynia than wild type (WT) mice in the destabilisation of medial meniscus model of OA. This was associated with a decreased suppression of inflammation by α7nAchR agonist. TgCHRFAM7A mice displayed a higher basal sensitivity to pain stimuli and increased pain behaviour in the monoiodoacetate and formalin models. Dorsal root ganglia of TgCHRFAM7A mice showed increased macrophage infiltration and expression of the chemokine fractalkine and also had a compromised antinociceptive response to the α7nAchR agonist nicotine. Both native CHRNA7 and CHRFAM7A subunits were expressed in human joint tissues and the CHRFAM7A/CHRNA7 ratio was increased in OA cartilage. Human chondrocytes with two copies of CHRFAM7A had reduced anti-inflammatory responses to nicotine.
conclusionCHRFAM7A is an aggravating factor for OA-associated inflammation and tissue damage and a novel genetic risk factor and therapeutic target for pain.
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