Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
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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.
ACS Appl Mater Interfaces 2013 Jul 10
PMID:Detection of ADAMTS-4 activity using a fluorogenic peptide-conjugated Au nanoparticle probe in human knee synovial fluid. 2371 7

The artificial joints, for example, knee and hip implants, are widely used for the treatment of degenerative joint diseases and trauma. The current most common material choice for clinically used implants is the combination of polymer-on-metal structures. Unfortunately, these joints often suffer from high friction and wear, leading to associated inflammation and infection and ultimate failure of the artificial joints. Here, we propose an alternative solution to this tribologically induced failure of the joint materials. We demonstrate that the friction and wear behavior of ultrahigh-molecular-weight polyethylene (UHMWPE) and titanium tribopair, used to mimic the artificial joint interface, can be improved by introducing nanodiamond (ND) particles in the sliding contact. Characterization of the wear track using energy-dispersive spectroscopy and Raman spectroscopy revealed that the tribofilm formed from embedded NDs during sliding significantly suppressed the wear of the UHMWPE surface. In addition to the improved lubrication characteristics, NDs exhibit high biocompatibility with the bone cells and promising antibacterial properties against Staphylococcus aureus, the most common strain associated with artificial joint infection. These results indicate that NDs can be used as a promising nontoxic human-body lubricant with antiwear and antibacterial features, thus demonstrating their great potential to treat artificial joint complications through intra-articular injection.
ACS Appl Mater Interfaces 2019 Nov 20
PMID:Combined Tribological and Bactericidal Effect of Nanodiamonds as a Potential Lubricant for Artificial Joints. 3165 39

Pyrophosphate arthropathy is the mineralization defect in humans caused by the deposition of microcrystals of calcium pyrophosphate dihydrate in joint tissues. As a potential therapeutic strategy for the treatment of pyrophosphate arthropathy, delivery of exogenous pyrophosphate-hydrolyzing enzymes, inorganic pyrophosphatases (PPases), to the synovial fluid has been suggested. Previously, we synthesized the conjugates of Escherichia coli PPase (Ec-PPase) with detonation synthesis nanodiamonds (NDs) as a delivery platform, obtaining the hybrid biomaterial retaining high pyrophosphate-hydrolyzing activity in vitro. However, most known PPases including Ec-PPase in the soluble form are strongly inhibited by Ca2+ ions. Because synovial fluid contains up to millimolar concentrations of soluble calcium, this inhibition might limit the in vivo application of Ec-PPase-based material in joint tissues. In this work, we proposed other bacterial PPases from Mycobacterium tuberculosis (Mt-PPase), which are resistant to the inhibition by Ca2+ ions, as an active PPi-hydrolyzing agent. We synthesized conjugates of Mt-PPase with NDs and tested their activity under various conditions. Unexpectedly, conjugates of both Ec-PPase and Mt-PPase with aminated NDs retained significant hydrolytic activity in the presence of well-known mechanism-based PPase inhibitors, fluoride or calcium. The incomplete inhibition of PPases by fluoride or calcium was found for the first time.
ACS Omega 2020 Mar 31
PMID:Synthesis of Inorganic Pyrophosphatase-Nanodiamond Conjugates Resistant to Calcium and Fluoride. 3225 99

The present work is focused on testing enzyme-based agents for the partial dissolution of calcium pyrophosphate (CaPPi) deposits in the cartilages and synovial fluid of patients with pyrophosphate arthropathy (CPPD disease). Previously, we suggested that inorganic pyrophosphatases (PPases) immobilized on nanodiamonds of detonation synthesis (NDs) could be appropriate for this purpose. We synthesized and characterized conjugates of NDs and PPases from Escherichia coli and Mycobacterium tuberculosis. The conjugates showed high enzymatic activity and resistance to inhibition by calcium and fluoride. Here, we tested the effectiveness of pyrophosphate (PPi) hydrolysis by the conjugates in an in vitro model system simulating the ionic composition of the synovial fluid and in the samples of synovial fluid of patients with CPPD via NMR spectroscopy. The conjugates of both PPases efficiently hydrolyzed triclinic crystalline calcium pyrophosphate (t-CPPD) in the model system. We evaluated the number of phosphorus-containing compounds in the synovial fluid, showed the possibility of PPi detection in it, and estimated the hydrolytic activity of the PPase conjugates. The soluble and immobilized PPases were able to hydrolyze a significant amount of PPi (1 mM) in the synovial fluid in short periods of time (24 h). The maximum activity was demonstrated for Mt-PPase immobilized on ND-NH-(CH2)6-NH2 (2.24 U mg-1).
ACS Omega 2020 Apr 21
PMID:Inorganic Pyrophosphatase-Nanodiamond Conjugates Hydrolyze Pyrophosphate in Human Synovial Fluid. 3233 20

Rheumatoid arthritis (RA) is an autoimmune disease that often causes progressive joint dysfunction, even disability and death in severe cases. The radical improvement of inflammatory cell infiltration and the resulting disorder in oxygen supply is a novel therapeutic direction for RA. Herein, a near-infrared-absorbing metal/semiconductor composite, polyethylene glycol-modified ceria-shell-coated gold nanorod (Au@CeO2), is fabricated for topical photothermal/oxygen-enriched combination therapy for RA in a mouse model. Upon laser irradiation, the photothermal conversion of Au@CeO2 is exponentially enhanced by the localized surface plasma resonance-induced light focusing. The elevated temperature can not only remarkably obliterate hyperproliferative inflammatory cells gathered in diseased joints but also vastly increase the catalase-like activity of ceria to accelerate the decomposition of H2O2 to produce much oxygen, which relieves hypoxia. Significantly, RA-induced lesions are improved, and the expression of proinflammatory cytokines and hypoxia-inducible factors is effectively repressed under the cooperation of heat and oxygen. Overall, the core/shell-structured Au@CeO2 is a promising nanotherapeutic platform that can well realize light-driven heat/oxygen enrichment to completely cure RA from the perspective of pathogenesis.
ACS Appl Mater Interfaces 2020 Oct 14
PMID:Near-Infrared Plasmon-Boosted Heat/Oxygen Enrichment for Reversing Rheumatoid Arthritis with Metal/Semiconductor Composites. 3293 Dec 33