Matrix Metalloproteases and Tissue Inhibitors of Metalloproteinases in Medial Plica and Pannus-like Tissue Contribute to Knee Osteoarthritis Progression

Chih-Chang Yang,Cheng-Yu Lin,Shaw-Ruey Lyu,Hwai-Shi Wang,Bart O Williams

doi:10.1371/journal.pone.0079662

Abstract

Osteoarthritis (OA) is characterized by degradation of the cartilage matrix, leading to pathologic changes in the joints. However, the pathogenic effects of synovial tissue inflammation on OA knees are not clear. To investigate whether the inflammation caused by the medial plica is involved in the pathogenesis of osteoarthritis, we examined the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the medial plica and pannus-like tissue in the knees of patients with medial compartment OA who underwent either arthroscopic medial release (stage II; 15 knee joints from 15 patients) or total knee replacement (stage IV; 18 knee joints from 18 patients). MMP-2, MMP-3, MMP-9, IL-1β, and TNF-α mRNA and protein levels measured, respectively, by quantitative real-time PCR and Quantibody human MMP arrays, were highly expressed in extracts of medial plica and pannus-like tissue from stage IV knee joints. Immunohistochemical staining also demonstrated high expression of MMP-2, MMP-3, and MMP-9 in plica and pannus-like tissue of stage IV OA knees and not in normal cartilage. Some TIMP/MMP ratios decreased significantly in both medial plica and pannus-like tissue as disease progressed from stage II to stage IV. Furthermore, the migration of cells from the pannus-like tissue was enhanced by IL-1β, while plica cell migration was enhanced by TNF-α. The results suggest that medial plica and pannus-like tissue may be involved in the process of cartilage degradation in medial compartment OA of the knee.

Highlights

Osteoarthritis (OA) is characterized by degradation of the cartilage matrix and gradually progresses without any repair of the damaged tissue, leading to pathologic changes in the joints
Since enzyme/inhibitor imbalance may result in excessive matrix degradation, we compared the ratio of tissue inhibitors of metalloproteinases (TIMPs)-1, TIMP-2, or TIMP-4 levels divided by matrix metalloproteinases (MMPs)-2, MMP-3, or MMP-4 levels in lysates of the two tissues in both sets of OA patients
MMP and TIMP mRNA expression in plica and pannuslike tissue from stage IV OA patients Since the ELISA array data showed that MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, and TIMP-4 proteins were highly expressed in plica and pannus-like tissues in stage IV patients (Figure 1A), we examined MMP and TIMP mRNA expression in these two tissues from stage IV OA patients and in normal cartilage by quantitative real-time PCR assay

Summary

Introduction

Osteoarthritis (OA) is characterized by degradation of the cartilage matrix and gradually progresses without any repair of the damaged tissue, leading to pathologic changes in the joints. Clinical symptoms in the OA knee include joint pain, inflammation, and functional disability of the joints. Synovial tissue inflammation was found to be a pathogenetic factor in the OA knee [5,6,7,8]. Since various degrees of cartilage degeneration on the surface of the medial femoral condyle facing the medial plica have been observed [14,16,17,18,19], a series of studies on medial plicarelated abrasion phenomenon were performed and provided evidence for a role of pathologic medial plica in the pathogenesis of medial compartment OA of the knee joint [15,20,21]

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Results

Conclusion