Detection of Active Matrix Metalloproteinase-3 in Serum and Fibroblast-Like Synoviocytes of Collagen-Induced Arthritis Mice

详细信息    查看全文

• 作者：Aeju Lee ; Sung-Jae Choi ; Kyeongsoon Park ; Jong Woong Park ; Kwangmeyung Kim ; Kuiwon Choi ; Soo-Young Yoon ; Inchan Youn
• 刊名：Bioconjugate Chemistry
• 出版年：2013
• 出版时间：June 19, 2013
• 年：2013
• 卷：24
• 期：6
• 页码：1068-1074
• 全文大小：343K
• 年卷期：v.24,no.6(June 19, 2013)
• ISSN：1520-4812

文摘

The activity of rheumatoid arthritis (RA) correlates with the expression of proteases. Among several proteases, matrix metalloproteinase-3 (MMP-3) is one of the biological markers used to diagnose RA. The active form of MMP-3 is a key enzyme involved in RA-associated destruction of cartilage and bone. Thus, detection of active MMP-3 in serum or in vivo is very important for early diagnosis of RA. In this study, a soluble MMP-3 probe was prepared to monitor RA progression by detecting expression of active MMP-3 in collagen-induced arthritis (CIA) mice in vivo in both serum and fibroblast-like synoviocytes (FLSs). The MMP-3 probe exhibited strong sensitivity to MMP-3 and moderate sensitivity to MMP-7 at nanomolecular concentrations, but was not sensitive to other MMPs such as MMP-2, MMP-9, and MMP-13. In an optical imaging study, the MMP-3 probe produced early and strong NIR fluorescence signals prior to observation of erythema and swelling in CIA mice. The MMP-3 probe was able to rapidly and selectively detect and monitor active MMP-3 in diluted serum from CIA mice. Furthermore, histological data demonstrated that activated FLSs in arthritic knee joints expressed active MMP-3. Together, our results demonstrated that the MMP-3 probe may be useful for detecting active MMP-3 for diagnosis of RA. More importantly, the MMP-3 probe was able to detect active MMP-3 in diluted serum with high sensitivity. Therefore, the MMP-3 probe developed in this study may be a very promising probe, useful as a biomarker for early detection and diagnosis of RA.