ArticleFibrogenesis & tissue repair2010
Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty.
Article in Fibrogenesis & tissue repair, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 97 citations in OpenAlex.
- Chronic Pain and Stiffness After Total Knee Arthroplasty: A Comprehensive, Phenotype-Based Review of Mechanisms, Diagnosis and Management.Journal of clinical medicine · 2026Review
- Novel tissue biomarker candidates to predict both deep venous thrombosis and healing outcome after Achilles tendon rupture.Scientific reports · 2025Article
- Fibroblasts in heterotopic ossification: mechanisms and therapeutic targets.International journal of biological sciences · 2025Review
- Uncommon, foreign-body induced knee arthrofibrosis in a pediatric patient.Trauma case reports · 2023Article
- Association between hyperlipidemia and trigger finger: A nationwide population-based cohort study.PloS one · 2023Article
- Immune cell populations differ in patients undergoing revision total knee arthroplasty for arthrofibrosis.Scientific reports · 2022Article
- Tourniquet use following blast-associated complex lower limb injury and traumatic amputation promotes end organ dysfunction and amplified heterotopic ossification formation.Journal of orthopaedic surgery and research · 2022Article
- Promising results of captopril in improving knee arthrofibrosis and cartilage status: an animal model study.Journal of experimental orthopaedics · 2022Article
- Sustained Delivery of SB-431542, a Type I Transforming Growth Factor Beta-1 Receptor Inhibitor, to Prevent Arthrofibrosis.Tissue engineering. Part A · 2021Article
- The effect of collagenase clostridium histolyticum on adhesion reduction in a rat knee arthrofibrosis model.Acta orthopaedica et traumatologica turcica · 2021Article
- A Rare Case of Extremely Severe Heterotopic Ossification after Primary Total Hip Arthroplasty due to Persistent Mild Periprosthetic Joint Infection.Case reports in orthopedics · 2021Article
- Postoperative Serum Cytokine Levels Are Associated With Early Stiffness After Total Knee Arthroplasty: A Prospective Cohort Study.The Journal of arthroplasty · 2020Article
- Increased elastic modulus of the synovial membrane in a rat ACLT model of osteoarthritis revealed by atomic force microscopy.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2020Article
- Chronic, Active Inflammation in Patients With Failed Total Knee Replacements Undergoing Revision Surgery.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2019Article
- The stiff total knee arthroplasty: causes, treatment modalities and results.EFORT open reviews · 2019Review
- All-arthroscopic release for treating severe knee extension contractures could improve the knee range of motion and the mid-term functional outcomes.Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA · 2019Article
- Carcinogenesis: the cancer cell-mast cell connection.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
- Low-grade infections as a possible cause of arthrofibrosis after total knee arthroplasty.Patient safety in surgery · 2019Article
- Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model.Drug design, development and therapy · 2019Article
- Pathological mechanisms and therapeutic outlooks for arthrofibrosis.Bone research · 2019Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIdiopathic arthrofibrosis occurs in 3-4% of patients who undergo total knee arthroplasty (TKA). However, little is known about the cellular or molecular changes involved in the onset or progression of this condition. To classify the histomorphologic changes and evaluate potential contributing factors, periarticular tissues from the knees of patients with arthrofibrosis were analyzed for fibroblast and mast cell proliferation, heterotopic ossification, cellular apoptosis, hypoxia and oxidative stress.
resultsThe arthrofibrotic tissue was composed of dense fibroblastic regions, with limited vascularity along the outer edges. Within the fibrotic regions, elevated numbers of chymase/fibroblast growth factor (FGF)-expressing mast cells were observed. In addition, this region contained fibrocartilage and associated heterotopic ossification, which quantitatively correlated with decreased range of motion (stiffness). Fibrotic, fibrocartilage and ossified regions contained few terminal dUTP nick end labeling (TUNEL)-positive or apoptotic cells, despite positive immunostaining for lactate dehydrogenase (LDH)5, a marker of hypoxia, and nitrotyrosine, a marker for protein nitrosylation. LDH5 and nitrotyrosine were found in the same tissue areas, indicating that hypoxic areas within the tissue were associated with increased production of reactive oxygen and nitrogen species.
conclusionsTaken together, we suggest that hypoxia-associated oxidative stress initiates mast cell proliferation and FGF secretion, spurring fibroblast proliferation and tissue fibrosis. Fibroblasts within this hypoxic environment undergo metaplastic transformation to fibrocartilage, followed by heterotopic ossification, resulting in increased joint stiffness. Thus, hypoxia and associated oxidative stress are potential therapeutic targets for fibrosis and metaplastic progression of idiopathic arthrofibrosis after TKA.
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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.