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

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.

Influence of Periostin on Synoviocytes in Knee Osteoarthritis

“…Our previous in vitro studies of human fibroblast-like synoviocytes suggest that elevated periostin levels mediate increases in the concentration of MMP-9 (15). Several studies have reported increases in the MMP-9 expression levels in knee synovial fluid during the progression of OA (32,33). The present study showed that the capacity of OA-associated synovial cells to produce MMP-2 and MMP-3 was enhanced by periostin stimulation (Figure 3A and B).…”

Knee health promotion option for knee osteoarthritis: A preliminary report of a concept of multidisciplinary management

“…Our further studies not only disclosed the kinematic relationship between the medial plica with the medial femoral condyle during knee motion in vivo [5], but also implied the close interplay between this structure and the medial femoral condyle [6]. More recently we have found [7,8] that the repeated injuries elicited by this abrasion phenomenon might trigger interleukin-1β (IL-1β) production in medial plica, thus enhancing the expression of matrix metalloproteinase-3 (MMP-3). Based on these findings, a concept of arthroscopic medial release (AMR) for the treatment of OA of the medial compartment of the knee joint was developed [9].…”

“…This global management concept was based on our understanding of the medial abrasion phenomenon as a cause of knee OA [4][5][6][7][8]. At follow-up after more than one year, patient satisfaction rate was 100% for patients who received arthroplasty, including 71 (8.4%) UKA and 116 (13.8%) TKA.…”

“…According to a recent qualitative study [20], providing adapted and formalized information to patients, adopting greater global assessment and more therapeutic approaches, and dealing more accurately with patients' paradoxical representations of therapy are key ways to improve the patient-physician relationship and the efficacy of treatment strategies. Based on our research and understanding about the medial abrasion phenomenon as a cause of pain and disability in most knee OA patients [4][5][6][7][8], our formalized global management protocol could provide precise and adequate information for both patients and health care providers.…”

“…1, which we call the "knee health promotion option (KHPO)", was implemented for the treatment of OA knees based on the findings of our previous research [4][5][6][7][8] regarding MAS as a cause of knee OA and the clinical outcome of ACRFP [10].…”