Abstract
BackgroundRheumatoid arthritis is a disease affecting the extracellular matrix of especially synovial joints. The thickness of the synovial membrane increases and surrounding tissue degrades, leading to altered collagen balance in the tissues. In this study, we investigated the altered tissue balance of cartilage, synovial membrane, and connective tissue in collagen induced arthritis (CIA) in rats.MethodsSix newly developed ELISAs quantifying MMP-derived collagen degradation (C1M, C2M, and C3M) and formation (P1NP, P2NP, and P3NP) was used to detect cartilage turnover in rats with CIA. Moreover, CTX-II was used to detect alternative type II collagen degradation and as control of the model. 10 Lewis rats were injected with porcrine type II collagen twice with a 7 day interval and 10 rats was injected with 0.05 M acetic acid as control. The experiment ran for 26 days.ResultsA significant increase in the degradation of type I, II, and III collagen (C1M, C2M, and C3M, respectively) was detected on day 22 (P = 0.0068, P = 0.0068, P < 0.0001, respectively), whereas no significant difference in formation (P1NP, P2NP, and P3NP) was detected at any time point (P=0.22, P=0.53, P=0.53, respectively). The CTX-II level increased strongly from disease onset and onwards.ConclusionA nearly total separation between diseased and control animals was detected with C3M, making it a good diagnostic marker. The balance of type I, II, and III collagen was significantly altered with CIA in rats, with favour of degradation of the investigated collagens. This indicates unbalanced turnover of the surrounding tissues of the synovial joints, leading to increased pain and degeneration of the synovial joints.
Highlights
Rheumatoid arthritis is a disease affecting the extracellular matrix of especially synovial joints
The synovial membrane is divided into two separate layers, an intimate layer of cells embedded in extra-cellular matrix (ECM) and a sub-intimae layer of loose connective tissue [8,9]
The increased amount of cells results in increased concentrations of degradative enzymes, such as matrix metalloproteinases (MMP) and aggrecanases, which are released into the synovial fluid, leading to increased degradation and formation of the surrounding ECM of cartilage, connective tissue, and the synovial membrane itself [11,12,13]
Summary
Rheumatoid arthritis is a disease affecting the extracellular matrix of especially synovial joints. We investigated the altered tissue balance of cartilage, synovial membrane, and connective tissue in collagen induced arthritis (CIA) in rats. Rheumatoid arthritis (RA) is a chronic inflammatory disease, which primarily affects the extra-cellular matrix (ECM) of the synovial joints [1]. The first layer consists of two types of cells, fibroblast-like synoviocytes and macrophages These cells form a capsule enclosing the joint, containing type I and III collagen [9,10]. The increased amount of cells results in increased concentrations of degradative enzymes, such as matrix metalloproteinases (MMP) and aggrecanases, which are released into the synovial fluid, leading to increased degradation and formation of the surrounding ECM of cartilage, connective tissue, and the synovial membrane itself [11,12,13]. These MMP’s are important proteolytic enzymes in ECM breakdown as MMP-1 degrades type I, II and III collagen, MMP-3 degrades, amongst other ECM proteins, type III collagen and the proteoglycans of cartilage, MMP-9 degrades type IV and V collagens, and MMP-13 degrades type I, II, and III collagen, type II collagen more efficiently than type I and III collagen
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