ArticleMolecular medicine (Cambridge, Mass.)2022
BNIP3 mediates the different adaptive responses of fibroblast-like synovial cells to hypoxia in patients with osteoarthritis and rheumatoid arthritis.
Article in Molecular medicine (Cambridge, Mass.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Global research trends in programmed cell death in rheumatoid arthritis from 2001 to 2025: a bibliometric analysis.Frontiers in immunology · 2026Pooled it
- The Role of Inflammation and Immunity in Cardiovascular Disease: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- NRAS and SREBF1 identified as mitophagy-associated risk genes for rheumatoid arthritis through interpretable machine learning and experimental validation studies.BMC rheumatology · 2026Article
- Multidimensional regulatory mechanisms and translational potential of epigenetic networks in the rheumatoid arthritis disease course.Frontiers in immunology · 2026Review
- Insights Into the HIF-1α-Mediated NLRP3 Pyroptosis Pathway in the Regulation of Musculoskeletal Diseases in the High-Altitude Environment.Journal of inflammation research · 2026Review
- Review
- BNIP3 induced by hypoxia supports the survival of mesenchymal stromal cells (MSCs) after intravenous cell transplantation.Regenerative therapy · 2025Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Article
- The role of hypoxic microenvironment in rheumatoid arthritis.Frontiers in immunology · 2025Review
- Emerging Therapeutic Targets in Rheumatoid Arthritis: Focusing on HIF-1α, Nrf2, STATs, and RORγt.Current drug targets · 2025Review
- ASIC1a Induces Excessive Mitophagy and PANoptosis of Chondrocyte by the Inhibition of SIRT3 Mitochondrial Translocation.Theranostics · 2025Article
- Advances in the study of mitophagy in osteoarthritis.Journal of Zhejiang University. Science. B · 2024Article
- Metabolic changes in fibroblast-like synoviocytes in rheumatoid arthritis: state of the art review.Frontiers in immunology · 2024Review
- Geniposide augments apoptosis in fibroblast-like synoviocytes by restoring hypoxia-enhanced JNK-BNIP3-mediated autophagy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Article
- Identification of a novel, MSC-induced macrophage subtype via single-cell sequencing: implications for intervertebral disc degeneration therapy.Frontiers in cell and developmental biology · 2023Article
- Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs.Frontiers in immunology · 2023Review
- Metabonomic analysis of abnormal sphingolipid metabolism in rheumatoid arthritis synovial fibroblasts in hypoxia microenvironment and intervention of geniposide.Frontiers in pharmacology · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypoxia is one of the important characteristics of synovial microenvironment in rheumatoid arthritis (RA), and plays an important role in synovial hyperplasia. In terms of cell survival, fibroblast-like synovial cells (FLSs) are relatively affected by hypoxia. In contrast, fibroblast-like synovial cells from patients with RA (RA-FLSs) are particularly resistant to hypoxia-induced cell death. The purpose of this study was to evaluate whether fibroblast-like synovial cells in patients with osteoarthritis (OA-FLSs) and RA-FLSs have the same adaptation to hypoxia.
methodsCCK-8, flow cytometry and BrdU were used to detect the proliferation of OA-FLSs and RA-FLSs under different oxygen concentrations. Apoptosis was detected by AV/PI, TUNEL and Western blot, mitophagy was observed by electron microscope, laser confocal microscope and Western blot, the state of mitochondria was detected by ROS and mitochondrial membrane potential by flow cytometry, BNIP3 and HIF-1α were detected by Western blot and RT-qPCR. The silencing of BNIP3 was achieved by stealth RNA system technology.
resultsAfter hypoxia, the survival rate of OA-FLSs decreased, while the proliferation activity of RA-FLSs further increased. Hypoxia induced an increase in apoptosis and inhibition of mitophagy in OA-FLSs, but not in RA-FLSs. Hypoxia led to a more lasting adaptive response. RA-FLSs displayed a more significant increase in the expression of genes transcriptionally regulated by HIF-1α. Interestingly, they showed higher BNIP3 expression than OA-FLSs, and showed stronger mitophagy and proliferation activities. BNIP3 siRNA experiment confirmed the potential role of BNIP3 in the survival of RA-FLSs. Inhibition of BNIP3 resulted in the decrease of cell proliferation, mitophagy and the increase of apoptosis.
conclusionIn summary, RA-FLSs maintained intracellular redox balance through mitophagy to promote cell survival under hypoxia. The mitophagy of OA-FLSs was too little to maintain the redox balance of mitochondria, resulting in apoptosis. The difference of mitophagy between OA-FLSs and RA-FLSs under hypoxia is mediated by the level of BNIP3 expression.
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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.