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Updated: Jun 26, 2026
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
MMP-3 activation is a hallmark indicating an early change in TMJ disorders, and is related to nitration
H Fujita1, T Morisugi, Y Tanaka
1Department of Oral and Maxillofacial Surgery, School of Medicine, Shimane University, Izumo, Shimane, Japan. omfshfjt@med.shimane-u.ac.jp
Abstract:
Recent studies on temporomandibular joint (TMJ) disorders have suggested that matrix metalloproteinases (MMPs) are closely involved in the pathophysiological progression of the internal derangement (ID) of TMJ. The aim of this study was to investigate MMPs in synovial fluid (SF) at different stages of ID. To examine the relationship between MMP activation and ID progression, 54 SF samples from ID patients were classified based on the criteria of Wilkes and were assayed for MMP activity. It was found that MMP-3 activity was transiently increased in the intermediate stage. This increase in the active form of MMP-3 was also confirmed by Western blotting. When the 54 samples were classified into two groups based on the presence or absence of inflammatory findings, the intensity of MMP-3 activity correlated with the inflammatory symptoms. These findings suggest that MMP-3 activation is a hallmark of early degenerative changes in ID. The tylosin nitration by the peroxynitrite can regulate the enzyme activity. To elucidate the activating pathway of MMPs in vivo, nitrated proteins in SF were analysed by immunoprecipitation. Some nitrated proteins in SF were identified as MMP-2 and -3, and the nitration of MMP-3 rendered them active in vitro.
Insights
Matrix metalloproteinase-3 (MMP-3) activation is linked to early temporomandibular joint (TMJ) internal derangement (ID) stages and inflammation. Peroxynitrite-mediated nitration activates MMP-3, suggesting a role in TMJ degenerative changes.
Area of Science:
- Biochemistry
- Orthodontics
- Rheumatology
Background:
- Temporomandibular joint (TMJ) disorders, particularly internal derangement (ID), involve complex pathophysiological processes.
- Matrix metalloproteinases (MMPs) are implicated in the progression of TMJ internal derangement.
Purpose of the Study:
- To investigate the activity and role of MMPs in synovial fluid (SF) across different stages of TMJ internal derangement.
- To explore the relationship between MMP activation, disease progression, and inflammatory markers in TMJ ID.
Main Methods:
- Analysis of 54 synovial fluid samples from TMJ ID patients, classified according to Wilkes criteria.
- Assay of MMP activity and confirmation of active MMP-3 using Western blotting.
- Immunoprecipitation to identify nitrated proteins, including MMP-2 and MMP-3, in synovial fluid.
Main Results:
- MMP-3 activity showed a transient increase in the intermediate stage of TMJ ID.
- Elevated MMP-3 activity correlated with the presence and intensity of inflammatory symptoms.
- Nitration of MMP-3 by peroxynitrite was shown to activate the enzyme in vitro.
Conclusions:
- MMP-3 activation appears to be a key indicator of early degenerative changes in TMJ internal derangement.
- Enzyme activity regulation by nitration, specifically involving peroxynitrite, is a potential pathway for MMP activation in vivo.
- These findings highlight MMP-3's role in the early pathogenesis of TMJ ID and suggest therapeutic targets.
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