ArticleAnnals of the New York Academy of Sciences2019
CITED2 mediates the cross-talk between mechanical loading and IL-4 to promote chondroprotection.
Article in Annals of the New York Academy of Sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Pooled it
- The role of exercise in MFN2 regulation in osteoarthritis.Molecular biology reports · 2026Review
- Article
- Osteoarthritis: Mechanisms and Therapeutic Advances.MedComm · 2025Review
- Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathway.Scientific reports · 2024Article
- RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling.Journal of orthopaedic translation · 2024Article
- Dysregulation of CITED2 in abnormal lung development in the nitrofen rat model.Pediatric surgery international · 2024Article
- The role of Th/Treg immune cells in osteoarthritis.Frontiers in immunology · 2024Review
- Identification of key biomarkers related to fibrocartilage chondrocytes for osteoarthritis based on bulk, single-cell transcriptomic data.Frontiers in immunology · 2024Article
- Transcriptomic analyses of joint tissues during osteoarthritis development in a rat model reveal dysregulated mechanotransduction and extracellular matrix pathways.Osteoarthritis and cartilage · 2023Article
- Bibliometric analysis of the inflammatory mechanisms in knee osteoarthritis in recent 30 years.American journal of clinical and experimental immunology · 2023Article
- Network-based modelling of mechano-inflammatory chondrocyte regulation in early osteoarthritis.Frontiers in bioengineering and biotechnology · 2023Article
- JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens.Frontiers in bioengineering and biotechnology · 2023Review
- Natural Compounds Affecting Inflammatory Pathways of Osteoarthritis.Antioxidants (Basel, Switzerland) · 2022Review
- MiR-659-3p inhibits osteosarcoma progression and metastasis by inhibiting cell proliferation and invasion via targeting SRPK1.BMC cancer · 2022Article
- The potential roles of JAK/STAT signaling in the progression of osteoarthritis.Frontiers in endocrinology · 2022Review
- Engineered Human Meniscus in Modeling Sex Differences of Knee OsteoarthritisFrontiers in bioengineering and biotechnology · 2022Article
- CircSNHG5 Sponges Mir-495-3p and Modulates CITED2 to Protect Cartilage Endplate From Degradation.Frontiers in cell and developmental biology · 2021Article
- Interplay of Forces and the Immune Response for Functional Tendon Regeneration.Frontiers in cell and developmental biology · 2021Review
- Comprehensive evaluation of differential long non-coding RNA and gene expression in patients with cartilaginous endplate degeneration of cervical vertebra.Experimental and therapeutic medicine · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Osteoarthritis (OA) pathogenesis is mediated largely through the actions of proteolytic enzymes such as matrix metalloproteinase (MMP) 13. The transcriptional regulator CITED2, which suppresses the expression of MMP13 in chondrocytes, is induced by interleukin (IL)-4 in T cells and macrophages, and by moderate mechanical loading in chondrocytes. We tested the hypothesis that CITED2 mediates cross-talk between IL-4 signaling and mechanical loading-induced pathways that result in chondroprotection, at least in part, by downregulating MMP13. IL-4 induced CITED2 gene expression in human chondrocytes in a dose- and time-dependent manner through JAK/STAT signaling. Mechanical loading combined with IL-4 resulted in additive effects on inducing CITED2 expression and downregulating of MMP13 in human chondrocytes in vitro. In vivo, IL-4 gene knockout (KO) mice exhibited reduced basal levels of CITED2 expression in chondrocytes. While moderate treadmill running induced CITED2 expression and reduced MMP13 expression in wild-type mice, these effects were blunted (for CITED2) or abolished (for MMP13) in chondrocytes of IL-4 gene KO mice. Moreover, intra-articular injections of mouse recombinant IL-4 combined with regular cage activity mitigated post-traumatic OA to a greater degree compared to immobilized mice treated with IL-4 alone. These data suggest that using moderate loading to enhance IL-4 may be a potential therapeutic strategy for chondroprotection in 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.