Matrix Metalloproteinase-dependent turnover of cartilage, synovial membrane, and connective tissue is elevated in rats w
- PDF / 249,832 Bytes
- 11 Pages / 595.28 x 793.7 pts Page_size
- 57 Downloads / 168 Views
RESEARCH
Open Access
Matrix Metalloproteinase-dependent turnover of cartilage, synovial membrane, and connective tissue is elevated in rats with collagen induced arthritis Anne Sofie Siebuhr1*, Jianxia Wang2, Morten Karsdal1, Anne-C Bay-Jensen1, Jin Y3 and Zheng Q4
Abstract Background: Rheumatoid 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. Methods: Six 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. Results: A 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. Conclusion: A 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. Keywords: Collagen balance, Rheumatoid arthritis, Matrix metalloproteinase, Synovial membrane, Cartilage, Connective tissue
Background Rheumatoid arthritis (RA) is a chronic inflammatory disease, which primarily affects the extra-cellular matrix (ECM) of the synovial joints [1]. The exact etiology of the disease is still unknown, but several factors such as gender [2], genetics [3,4] and antigens [1] are thought to be involved. The extensive inflammation of the synovial membrane (i.e. synovitis) and other joint tissues induces * Correspondence: [email protected] 1 Nordic Bioscience, Herlev, Denmark Full list of author information is available at the end of the article
secretion of proteolytic enzymes leading to degradation of cartilage and elevated bone turnover [5-7]. The synovial membrane is divided into two separate layers, an intimate layer of cells embedded in ECM and a sub-intimae layer of loose connective tissue [8,9]. The first layer consists of two types of cells, fibroblast-like synoviocytes and macrophages. These cells form a capsule encl
Data Loading...
