ArticleFibrogenesis & tissue repair2009
Reactive oxygen and nitrogen species induce protein and DNA modifications driving arthrofibrosis following total knee arthroplasty.
Article in Fibrogenesis & tissue repair, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 81 citations in OpenAlex.
- Vitamin C demand is increased after total knee arthroplasty: a double-blind placebo-controlled-randomized study.Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA · 2019Trial
- Chronic Pain and Stiffness After Total Knee Arthroplasty: A Comprehensive, Phenotype-Based Review of Mechanisms, Diagnosis and Management.Journal of clinical medicine · 2026Review
- Natural course of postoperative C-reactive protein and erythrocyte sedimentation rate in unilateral and simultaneous bilateral total knee arthroplasty.BMC musculoskeletal disorders · 2025Article
- The epigenetic regulator BRD4 is required for myofibroblast differentiation of knee fibroblasts.Journal of cellular biochemistry · 2023Article
- Hesperidin Methyl Chalcone Reduces the Arthritis Caused by TiOMolecules (Basel, Switzerland) · 2023Article
- Biochemical markers of postsurgical knee arthrofibrosis: A systematic review.Journal of orthopaedics · 2023Review
- Human outgrowth knee fibroblasts from patients undergoing total knee arthroplasty exhibit a unique gene expression profile and undergo myofibroblastogenesis upon TGFβ1 stimulation.Journal of cellular biochemistry · 2022Article
- Arthrofibrosis of the Ankle.Foot & ankle orthopaedics · 2020Review
- Article
- Postoperative Serum Cytokine Levels Are Associated With Early Stiffness After Total Knee Arthroplasty: A Prospective Cohort Study.The Journal of arthroplasty · 2020Article
- Proteoglycan-4 regulates fibroblast to myofibroblast transition and expression of fibrotic genes in the synovium.Arthritis research & therapy · 2020Article
- The Comparison of Parameters of Oxidative Stress in Native Rat Livers Between Different Immunosuppressive Regimens.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Low-grade infections as a possible cause of arthrofibrosis after total knee arthroplasty.Patient safety in surgery · 2019Article
- Increased Risk of Heterotopic Ossification Following Revision Hip Arthroplasty for Periprosthetic Joint Infection.The archives of bone and joint surgery · 2018Article
- A Systems Biology Approach for Studying Heterotopic Ossification: Proteomic Analysis of Clinical Serum and Tissue Samples.Genomics, proteomics & bioinformatics · 2018Article
- Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives.Medical sciences (Basel, Switzerland) · 2018Review
- The role of monocytosis and neutrophilia in atherosclerosis.Journal of cellular and molecular medicine · 2018Review
- Total Knee Arthroplasty in Patients with Retention of Prior Hardware Material: What is the Outcome?The archives of bone and joint surgery · 2018Article
- Adverse Biological Effect of TiO₂ and Hydroxyapatite Nanoparticles Used in Bone Repair and Replacement.International journal of molecular sciences · 2016Review
- Predominance of synovial sensory nerve fibers in arthrofibrosis following total knee arthroplasty compared to osteoarthritis of the knee.Journal of orthopaedic surgery and research · 2016Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundArthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA), is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS) and nitrogen species (RNS) mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation.
resultsWe found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed in both macrophages and fibroblasts in arthrofibrotic tissue. As direct measurement of ROS/RNS is not feasible, products including DNA hydroxylation (8-OHdG), and protein nitrosylation (nitrotyrosine) were measured by immunohistochemistry. Quantification of the staining showed that 8-OHdg was significantly increased in arthrofibrotic tissue. There was also a direct correlation between the intensity of inflammation and ROS/RNS to the amount of heterotopic ossification (HO). In order to investigate the aberrant expression of MPO, a real-time oxidative stress polymerase chain reaction array was performed on fibroblasts isolated from arthrofibrotic and control tissues. The results of this array confirmed the upregulation of MPO expression in arthrofibrotic fibroblasts and highlighted the downregulated expression of the antioxidants, superoxide dismutase1 and microsomal glutathione S-transferase 3, as well as the significant increase in thioredoxin reductase, a known promoter of cell proliferation, and polynucleotide kinase 3'-phosphatase, a key enzyme in the base excision repair pathway for oxidative DNA damage.
conclusionBased on our current findings, we suggest that ROS/RNS initiate and sustain the arthrofibrotic response driving aggressive fibroblast proliferation and subsequent HO.
Identifiers
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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.