Abstract
Osteoarthritis (OA) is the leading cause of chronic disability affecting the elderly. There is an acute demand for novel approaches to sensitively and specifically detect OA biomarkers in conjunction with traditional radiographic outcomes to facilitate early diagnosis and allow timely treatment. In this study, a novel strategy is introduced to detect the activity of matrix metallopeptidase 13 (MMP-13)—a key enzyme responsible for cartilage matrix degradation in OA with a synthesized molecular probe containing a hydrophilic MMP-13-sensitive peptide conjugated to an aggregation induced emission fluorogen (AIEgen). The MMP-13 cleaves the MMP-13 sensitive peptide and induces aggregation of the hydrophogic AIEgen residues resulting in the activation of a fluorescent signal. The results demonstrate that this probe can detect increasing MMP-13 activity, which is an important marker of osteogenic differentiation in living and differentiating stem cells. This allows easy and semi-quantitative assessment of the extent of stem cell differentiation. Furthermore, by administering this probe to diseased joints of rats with induced OA, the real-time detection of MMP-13 activity is demonstrated in the osteoarthritic knee joints of living animals. It is believed that the molecular probe is a promising tool for real-time detection of disease markers with high fluorescence contrast to aid the early diagnosis of OA.
Original language | English |
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Article number | 1800010 |
Journal | Advanced Biosystems |
Volume | 2 |
Issue number | 10 |
DOIs | |
Publication status | Published - Oct 2018 |
Keywords
- aggregation-induced emission
- enzyme cleavage
- enzyme sensitive peptide
- matrix metalloproteinase 13
- osteoarthritis detection
ASJC Scopus subject areas
- Biomaterials
- Biomedical Engineering
- General Biochemistry,Genetics and Molecular Biology