Browsing by Subject "Matrix metalloproteinase"
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Item Doxycycline-loaded nanotube-modified adhesives inhibit MMP in a dose-dependent fashion(Springer Nature, 2018-04) Palasuk, Jadesada; Windsor, L. Jack; Platt, Jeffrey A.; Lvov, Yuri; Geraldeli, Saulo; Bottino, Marco C.; Biomedical Sciences and Comprehensive Care, School of DentistryOBJECTIVES: This article evaluated the drug loading, release kinetics, and matrix metalloproteinase (MMP) inhibition of doxycycline (DOX) released from DOX-loaded nanotube-modified adhesives. DOX was chosen as the model drug, since it is the only MMP inhibitor approved by the U.S. Food and Drug Administration. MATERIALS AND METHODS: Drug loading into the nanotubes was accomplished using DOX solution at distinct concentrations. Increased concentrations of DOX significantly improved the amount of loaded DOX. The modified adhesives were fabricated by incorporating DOX-loaded nanotubes into the adhesive resin of a commercial product. The degree of conversion (DC), Knoop microhardness, DOX release kinetics, antimicrobial, cytocompatibility, and anti-MMP activity of the modified adhesives were investigated. RESULTS: Incorporation of DOX-loaded nanotubes did not compromise DC, Knoop microhardness, or cell compatibility. Higher concentrations of DOX led to an increase in DOX release in a concentration-dependent manner from the modified adhesives. DOX released from the modified adhesives did not inhibit the growth of caries-related bacteria, but more importantly, it did inhibit MMP-1 activity. CONCLUSIONS: The loading of DOX into the nanotube-modified adhesives did not compromise the physicochemical properties of the adhesives and the released levels of DOX were able to inhibit MMP activity without cytotoxicity. CLINICAL SIGNIFICANCE: Doxycycline released from the nanotube-modified adhesives inhibited MMP activity in a concentration-dependent fashion. Therefore, the proposed nanotube-modified adhesive may hold clinical potential as a strategy to preserve resin/dentin bond stability.Item Matrix metalloproteinases in preterm prelabor rupture of membranes in the setting of chorioamnionitis: A scoping review(Wiley, 2023) Nguyen, Lynsa M.; Aronoff, David M.; Eastman, Alison J.; Medicine, School of MedicineFetal or gestational membranes extend from the placenta to enclose the fetus and amniotic fluid. While the membranes spontaneously rupture at term in normal pregnancies, they can rupture prematurely before the onset of labor, termed preterm prelabor rupture of membranes (PPROM). PPROM can be triggered by bacterial infection or sterile inflammation in the membranes, known as chorioamnionitis (CAM). The membranes derive their tensile strength from a collagen-rich extracellular matrix (ECM); as such, understanding the enzymes and processes that can degrade the membrane ECM are of paramount importance. Matrix metalloproteinases (MMPs) are a class of enzymes capable of degrading collagen and other components of the ECM, and can be induced by inflammation. We used a scoping review to address the question of how MMP activity is associated with PPROM, particularly their induction due to sterile or nonsterile CAM. We have found that the most studied MMPs in PPROM were MMPs 2, 8, and 9. Additionally, some MMPs are constitutively active, while others are induced by inflammation. Mechanistic studies of the pathways that induce MMP activation are sparse, and this area is ripe for future studies. Targeting MMP activation could be a future strategy to delay or prevent PPROM.Item Moderate joint loading reduces degenerative actions of matrix metalloproteinases in the articular cartilage of mouse ulnae(Taylor & Francis, 2012) Sun, Hui B.; Zhao, Liming; Tanaka, Shigeo; Yokota, Hiroki; Department of Biomedical Engineering, School of Engineering and TechnologyJoint loading is a recently developed loading modality, which can enhance bone formation and accelerate healing of bone fracture. Since mechanical stimulation alters expression of matrix metalloproteinases (MMPs) in chondrocytes, a question addressed herein was, does joint loading alter actions of MMPs in the articular cartilage? We hypothesized that expression and activity of MMPs are regulated in a load-intensity-dependent manner and that moderate load scan downregulates MMPs. To test this hypothesis, a mouse elbow-loading model was employed. In the articular cartilage of an ulna, the mRNA levels of a group of MMPs as well as their degenerative activities were determined. The result revealed that elbow loading altered the expression and activities of MMPs depending on its loading intensity. Collectively, the data in this study indicate that 0.2 and 0.5 N joint loading significantly reduced the expression of multiple MMPs, that is, MMP-1, MMP-3, MMP-8, and MMP-13, and overall activities of collagenases or gelatinases in articular cartilage, while higher loads increased the expression and activity of MMP-1 and MMP-13. Furthermore, moderate loads at 1 N elevated the mRNA level of CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), but higher loads at 4 N did not induce a detectable amount of CITED2 mRNA. Since CITED2 is known to mediate the downregulation of MMP-1 and MMP-13, the result indicates that joint loading at moderate intensity reduces MMP activities through potential induction of CITED2. MMPs such as MMP-1 and MMP-13 are predominant collagenases in the pathology of osteoarthritis. Therefore, joint loading could offer an interventional regimen for maintenance of joint tissues.Item Physicochemical and Biological Properties of Novel Chlorhexidine-Loaded Nanotube-Modified Dentin Adhesive(Wiley, 2018-09-10) Feitosa, Sabrina A.; Palasuk, Jadesada; Geraldeli, Saulo; Windsor, L. Jack; Bottino, Marco C.; Biomedical Sciences and Comprehensive Care, School of DentistryA commercially available three-step (etch-and-rinse) adhesive was modified by adding chlorhexidine (CHX)-loaded nanotubes (Halloysite®, HNT) at two concentrations (CHX10% and CHX20%). The experimental groups were: SBMP (unmodified adhesive, control), HNT (SBMP modified with HNT), CHX10 (SBMP modified with HNT loaded with CHX10%), and CHX20 (SBMP modified with HNT loaded with CHX20%). Changes in the degree of conversion (DC%), Knoop hardness (KHN), water sorption (WS), solubility (SL), antimicrobial activity, cytotoxicity, and anti-matrix metalloproteinase [MMP-1] activity (collagenase-I) were evaluated. In regards to DC%, two-way ANOVA followed by Tukey’s post-hoc test revealed that only the factor “adhesive” was statistically significant (p<0.05). No significant differences were detected in DC% when 20 s light-curing was used (p>0.05). For Knoop microhardness, one-way ANOVA followed by the Tukey’s test showed statistically significant differences when comparing HNT (20.82±1.65) and CHX20% (21.71±2.83) with the SBMP and CHX10% groups. All adhesives presented similar WS and cytocompatibility. The CHX-loaded nanotube-modified adhesive released enough CHX to inhibit the growth of S. mutans and L. casei. Adhesive eluates were not able to effectively inhibit MMP-1 activity. The evaluation of higher CHX concentrations might be necessary to provide an effective and predictable MMP inhibition.