PMID- 33405657 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210106 IS - 2373-9878 (Electronic) IS - 2373-9878 (Linking) VI - 5 IP - 6 DP - 2019 Jun 10 TI - Fluorogenic Probe for Detecting Active Matrix Metalloproteinase-3 (MMP-3) in Plasma and Peripheral Blood Neutrophils to Indicate the Severity of Rheumatoid Arthritis. PG - 3039-3048 LID - 10.1021/acsbiomaterials.9b00084 [doi] AB - Diagnosis of patients with rheumatoid arthritis (RA) is essential for early and accurate drug treatment to protect the patient from joint bone erosion and relieve symptoms of the disease. In some cases, the RA patient's X-ray images and other clinical diagnostic methods are often difficult to distinguish from different diseases, such as gout, osteoarthritis, and other inflammatory conditions. Thus, methods for diagnosis of disease activity and real-time monitoring of therapeutic effect and accurate differentiation from other bone diseases are needed. In this article, we suggest a matrix metalloproteinase-3 (MMP-3)-specific protease-activated probe immobilized in vitro kit and cell staining for flow cytometry analysis as methods to support clinical diagnosis. To overcome interindividual differences, we used phorbol 12-myristate 13-acetate (PMA)-activated plasma from 269 RA patients, 49 osteoarthritis patients, and 30 healthy volunteers. The in vitro kit developed for PMA-activated plasma showed potential for identifying disease severity and distinguishing RA from other bone diseases. In particular, expression of active MMP-3 increased until the moderate disease activity and then sharply decreased at severe disease. We suggest an analysis of intracellular MMP-3-specific protease-activated probe staining by flow cytometry. Compared with anti-MMP-3 antibody staining, the results for active MMP-3 in neutrophils using the probe exactly matched the results obtained with the in vitro kit. We also confirmed that expression of active MMP-3 was mainly from neutrophils. Together, these results suggest that the MMP-3-specific protease-activated probe might be a promising noninvasive tool for accurate diagnosis of disease severity and differentiation from similar bone diseases as well as for monitoring therapeutic efficacy. FAU - Lee, Ruda AU - Lee R AD - International Research Organization for Advanced Science and Technology (IROAST), Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto, 860-8555, Japan. AD - Magnesium Research Center (MRC), Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto, 860-8555, Japan. FAU - Choi, Sung-Jae AU - Choi SJ AD - Department of Internal Medicine, Division of Rheumatology, College of Medicine, Korea University, 516 Danwon-gu, Ansan, 15355, Republic of Korea. FAU - Moon, Kyung Chul AU - Moon KC AD - Department of Laboratory Medicine, College of Medicine, Korea University, 148 Gurodong-ro, Guro-ku, Seoul, 08308, Republic of Korea. FAU - Park, Jong Woong AU - Park JW AD - Department of Orthopedic Surgery, College of Medicine, Korea University, Anam-dong 5-ga, Seongbuk-gu, Seoul, 02841, Republic of Korea. FAU - Kim, Kwangmeyung AU - Kim K AUID- ORCID: 0000-0001-7919-188X AD - Biomedical Research Center, Korea Institute of Science and Technology, 5. Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea. FAU - Yoon, Soo-Young AU - Yoon SY AD - Department of Laboratory Medicine, College of Medicine, Korea University, 148 Gurodong-ro, Guro-ku, Seoul, 08308, Republic of Korea. FAU - Youn, Inchan AU - Youn I AUID- ORCID: 0000-0002-0977-0808 AD - Biomedical Research Center, Korea Institute of Science and Technology, 5. Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea. LA - eng PT - Journal Article DEP - 20190528 PL - United States TA - ACS Biomater Sci Eng JT - ACS biomaterials science & engineering JID - 101654670 SB - IM OTO - NOTNLM OT - blood cell activation OT - matrix metalloproteinase-3 OT - neutrophils OT - protease-activated sensor OT - rheumatoid arthritis EDAT- 2019/06/10 00:00 MHDA- 2019/06/10 00:01 CRDT- 2021/01/06 17:10 PHST- 2021/01/06 17:10 [entrez] PHST- 2019/06/10 00:00 [pubmed] PHST- 2019/06/10 00:01 [medline] AID - 10.1021/acsbiomaterials.9b00084 [doi] PST - ppublish SO - ACS Biomater Sci Eng. 2019 Jun 10;5(6):3039-3048. doi: 10.1021/acsbiomaterials.9b00084. Epub 2019 May 28.