1 research outputs found
Detection of ADAMTS‑4 Activity Using a Fluorogenic Peptide-Conjugated Au Nanoparticle Probe in Human Knee Synovial Fluid
A disintegrin
and metalloproteinase with thrombospondin motif-4
(ADAMTS-4) plays a pivotal role in degrading aggrecan, which is an
early event in cartilage degrading joint diseases such as osteoarthritis
(OA). Detection of ADAMTS-4 activity could provide useful clinical
information for early diagnosis of such diseases and disease-modifying
therapy. Therefore, we developed a ADAMTS-4 detective fluorescent
turn-on AuNP probe (ADAMTS-4-D-Au probe) by conjugating gold nanoparticles
with a FITC-modified ADAMTS-4-specific peptide (DVQEFRGVTAVIR). When
the ADAMTS-4-D-Au probe was incubated with ADAMTS-4, the fluorescence
recovered and fluorescence intensity markedly increased in proportion
to concentrations of ADAMTS-4 and the probe. A nearly 3-fold increase
in fluorescent intensity in response to only 3.9 pM of ADAMTS-4 was
detected, whereas almost no fluorescence recovery was observed when
the probe was incubated with matrix metalloproteinase (MMP)-1, -3,
and -13. These results indicate a relative high sensitivity and specificity
of the probe. Moreover, ADAMTS-4-D-Au probe was used to detect ADAMTS-4
activity in synovial fluid from 11 knee surgery patients. A substantial
increase in fluorescent intensity was observed in the acute joint
injury group as compared to the chronic joint injury and end-stage
OA groups, indicating that this simple and low-cost sensing system
might serve as a new detection method for ADAMTS-4 activity in biological
samples and in screens for inhibitors for ADAMTS-4-related joint diseases.
Additionally, this probe could be a potential biomarker for early
diagnosis of cartilage-degrading joint diseases