Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty.

Authors

Theresa A Freeman, Department of Orthopaedic Surgery, Thomas Jefferson University, 1015 Walnut Street, Suite 501, Philadelphia, PA 19107, USAFollow
Javad Parvizi, The Rothman Institute of Orthopedics at Thomas Jefferson University, 925 Chestnut Street, Philadelphia, PA 19107, USAFollow
Craig J Dela Valle, Department of Orthopaedic Surgery, Rush University Medical Center, 1725 W. Harrison Street, Suite 1063, Chicago, IL 60612, USA
Marla J Steinbeck, School of Biomedical Engineering and College of Drexel Medicine, Drexel University, 3120 Market Street, 323 Bossone, Philadelphia, PA 19104, USAFollow

Document Type

Article

Publication Date

1-1-2010

Comments

This article has been peer reviewed and is published in BMC Fibrogenesis & Tissue Repair 2010, 3:17. The published version is available at . Copyright © BioMed Central Ltd.

Abstract

ABSTRACT: BACKGROUND: Idiopathic 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. RESULTS: The 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. CONCLUSIONS: Taken 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.

Recommended Citation

Freeman, Theresa A; Parvizi, Javad; Dela Valle, Craig J; and Steinbeck, Marla J, "Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty." (2010). Department of Orthopaedic Surgery Faculty Papers. Paper 27.
https://jdc.jefferson.edu/orthofp/27

PubMed ID

20809936