title: Detection of active matrix metalloproteinase-3 in serum and fibroblast-like synoviocytes of collagen-induced arthritis mice.
abstract: 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.
authors.affiliation: Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-Dong, Seongbuk-gu, Seoul 136-791, South Korea.
authors.forename: Aeju
authors.initials: A
authors.lastname: Lee
authors.forename: Sung-Jae
authors.initials: SJ
authors.lastname: Choi
authors.forename: Kyeongsoon
authors.initials: K
authors.lastname: Park
authors.forename: Jong Woong
authors.initials: JW
authors.lastname: Park
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Yoon
authors.forename: Inchan
authors.initials: I
authors.lastname: Youn
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000201:enzymology* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000201:enzymology* / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D004789:Enzyme Activation; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D057054:Molecular Imaging; D013583:Synovial Membrane / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism
chemical_list: D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse