Effect Of Matrix Metalloproteinase Inhibitor Research Articles

Effect of matrix metalloproteinase inhibitors on microtensile bond strength to dentin using self-etch adhesive - in vivo study

Effect of matrix metalloproteinase inhibitors on microtensile bond strength to dentin using self-etch adhesive - in vivo study

Effect of matrix metalloproteinase inhibitors on bonding durability of universal adhesives.

This study aimed to evaluate the effect of different matrix metalloproteinase inhibitors (MMPIs) on the microtensile bond strength (μTBS) and nanoleakage of universal adhesives. One hundred twenty non-carious human molars were prepared and randomly assigned to two groups: Scotchbond Bond Universal (SBU) and Gluma Bond Universal (GBU). The samples in each group were assigned to five subgroups (n=12) based on one control (water) and four MMPIs (Benzalkonium-chloride (BAC), Batimastat (BB94), Chlorhexidine (CHX), and Epigallocatechin-gallate (EGCG)). Each adhesive was applied in self-etch (SE) mode or etch-and-rinse (ER) mode. Dentin/composite sticks were fabricated and subjected to the μTBS test after 24 h or 6 months. At 6 months, MMPIs did not affect the μTBS of the adhesives, regardless of etching mode. Nanoleakage was more pronounced in ER mode than in SE mode for all subgroups. All MMPIs, with the exception of CHX, decreased the nanoleakage of GBU in ER mode.

Effect of MMP Inhibitors on the Bond Strength of Fibre Posts After Ageing

AimThis in vitro study aimed to evaluate the effect of matrix metalloproteinase (MMP) inhibitors on the bond strength of resin-cemented fibre posts to radicular dentin under an aged-loaded condition. Materials and methodsRadicular dentin was prepared and irrigated by MMP inhibitor solution after root canal obturation in 60 extracted single-rooted teeth based on 6 groups: (1) 2% chlorhexidine (CHX) + loaded; (2) CHX + unloaded; (3) 0.5% benzalkonium chloride (BAC) + loaded; (4) BAC + unloaded; (5) 17% ethylenediaminetetraacetic acid (EDTA) + loaded; and (6) EDTA + unloaded. After final rinsing, all specimens were sliced cross-sectionally and kept in a water bath for 12 months of ageing. Groups 1, 3, and 5 were subjected to cyclic loading. Push-out tests were conducted using a universal testing machine, and failure mode was examined. The data were analysed using 3-way analysis of variance and post hoc tests at α = 0.05. ResultsBAC + unloaded demonstrated the highest mean bond strength (3.12 ± 0.18 MPa; P < .001), while the BAC + loaded and CHX + loaded groups showed a significantly lower push-out bond strength than their unloaded counterparts. Mixed adhesive-cohesive failure was the most common failure mode observed. ConclusionsWithout cycling loading, BAC was superior to CHX and EDTA in preserving the bond strength of resin-cemented fibre posts after 12 months of ageing. Loading significantly weakened the effectiveness of BAC and CHX in preserving the bond strength.

The Effect of Matrix Metalloproteinase Inhibitors on the Microtensile Bond Strength of Dentin Bonding Agents in Caries Affected Dentin: A Systematic Review.

Matrix metalloproteinases (MMPs) cause degradation of the dentinal matrix, as they act actively on collagen fibrils, leading to their deterioration and collapse. MMP inhibitors are known to be used for the pre-treatment of human dentin before bonding. Most studies on the MMP inhibitors examined the effect of MMP inhibitors on bonding to sound dentin (SD), but few examine their effect on bonding to caries affected dentin (CAD). This systematic review aims to identify and summarize studies that have applied MMP inhibitors for pre-treatment of CAD, and examine the microtensile bond strength (µTBS), bond durability, and the mode of failure. A systematic review was performed using the PubMed database according to the PRISMA guidelines. A total of 785 original articles published between 2010 and 2022 were initially retrieved. Six studies were selected based on predefined inclusion-exclusion criteria, and their outcomes were extracted and analyzed. The methodological quality assessment was performed using a combined checklist that utilizes the reporting criteria mentioned in the checklist for reporting in-vitro studies guidelines and guidelines for reporting pre-clinical in vitro studies on dental materials. All six studies included here showed a definitive increase of the µTBS when MMP inhibitors were applied to the CAD. The mode of failure was found to be predominantly adhesive in nature. The deviation in the values of µTBS was approximately 2-5 MPa on immediate and delayed testing. MMP-inhibiting agents could be considered for the pretreatment of teeth with CAD as a part of their tooth preparation area, thereby allowing the clinician to retain CAD and bond to the CAD without endangering the vital pulp.

Effect of matrix metalloproteinase inhibitors on microtensile bond strength of dental composite restorations to dentin in use of an etch-and-rinse adhesive system.

AimThis study assesses the effect of matrix metalloproteinases on microtensile bond strength (μTBS) of an etch‐and‐rinse adhesive system.MethodsThis in vitro study evaluated 88 extracted premolars. The teeth were sectioned to expose dentin and were then randomly divided into four groups (n = 22). In group 1 (control), dentin surface was etched, and Adper Single Bond 2 was applied. In groups 2–4, dentin surface was etched and chlorhexidine (CHX), 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC), and dimethyl sulfoxide (DMSO) were applied on the surfaces, respectively, and blotted dry. Next, Adper Single Bond 2 was applied and all teeth were built up with Z350 composite. In each group, half the samples immediately and the other half after 10,000 thermal cycles underwent μTBS test. Data were analyzed using ANOVA and Tukey's test (α = .05).ResultsIn thermocycled samples, maximum μTBS was noted in CHX group followed by DMSO, EDC, and control group (p < .001). The thermocycled μTBS of composite to dentin was significantly higher in CHX group compared with EDC, DMSO, and control groups (p < .001) but was not significantly different in EDC and DMSO groups (p = .498).ConclusionThe thermocycled μTBS obtained by the application of CHX, EDC, and DMSO was significantly higher compared with the value to the control group.

Noise-induced blood-labyrinth-barrier trauma of guinea pig and the protective effect of matrix metalloproteinase inhibitors

Objective: The research is to study the expression and distribution of matrix metalloproteinase (MMPs)-2 and -9 in the guinea pig cochlea after noise exposure, and to explore the role of MMPs in the blood-labyrinth-barrier (BLB). In addition, the role of MMPs inhibitor doxycycline in noise-induced BLB trauma was studied as well, which provides the basis for further studies and prophylaxis of noise-induced hearing loss. Methods: A total of 45 healthy adult guinea pigs were randomly divided into the control group (15 received intraperitoneal injection of 0.9% saline for 4 consecutive days), the noise-exposure group (15 exposed by 120 dB SPL white noise for 4 h per day for continuous 2 d, intraperitoneal injection of normal saline for 4 consecutive days) and the noise-exposure + doxycycline group (15 exposed by 120 dB SPL white noise exposure for 4 h per day for 2 consecutive days, and intraperitoneal injection of doxycycline 50 mg/kg/d for 4 consecutive days), respectively. Immunofluorescence staining, western blot, and real-time quantitative PCR were used to analyze the distribution and differential expression of MMP-2 and -9 in the stria vascularis of guinea pigs in comparison with the normal control group, noise only group, and noise & doxycycline treatment group. Immunofluorescence staining was used to observe the changes in tight junction (TJ) protein ZO-1 in stria vascularis in three groups and to investigate the effect of acoustic injury on TJs. And ABR tests were utilized to detect the hearing function of guinea pigs in the three groups. Intravenous Evans blue was administrated intravenously as an indicator of vascular leakage among three groups to study the changes in BLB permeability in context of acoustic injury. SPSS 22.0 was used for statistical analysis. Results: There was no significant difference in hearing function between the noise-exposure group and the noise & doxycycline group two hours after noise exposure. After seven, 14 and 28 days noise exposure, the hearing recovery of the noise & doxycycline treatment group was significantly greater than that of the noise-exposure group (P<0.05) . Immunofluorescence staining showed that there was only a small amount of MMP-2 and -9 in the stria vascular in the normal control group, and ZO-1 showed dense linear expression. While, in the noise-explore group, MMP-2 and -9 in the stria vascular was significantly elevated (P<0.05), and the configuration of ZO-1 became loose and discontinuous. However, the MMP-2 and -9 in the noise & doxycycline treatment group were not significantly different from the normal control group (P>0.05), which were significantly less than that in the noise-exposure group, and just a little break of ZO-1 was observed, however, the overall structure remained dense. The leakage of Evans blue from stria vascular capillary in the noise-exposure group was significantly increased, and the difference between the other two groups did not show any statistical significance (P>0.05). Conclusions: The damage of tight junction structure induced by MMP-2 and -9 may play an important role in BLB destruction. In addition, doxycycline can inhibit MMPs secretion, thereby, to some extent, protecting the integrity of BLB from acoustic injury, and contributing to the long-term hearing recovery.

Tetraspanin-6 negatively regulates exosome production

Exosomes, extracellular vesicles (EVs) of endosomal origin, emerge as master regulators of cell-to-cell signaling in physiology and disease. Exosomes are highly enriched in tetraspanins (TSPNs) and syndecans (SDCs), the latter occurring mainly in proteolytically cleaved form, as membrane-spanning C-terminal fragments of the proteins. While both protein families are membrane scaffolds appreciated for their role in exosome formation, composition, and activity, we currently ignore whether these work together to control exosome biology. Here we show that TSPN6, a poorly characterized tetraspanin, acts as a negative regulator of exosome release, supporting the lysosomal degradation of SDC4 and syntenin. We demonstrate that TSPN6 tightly associates with SDC4, the SDC4-TSPN6 association dictating the association of TSPN6 with syntenin and the TSPN6-dependent lysosomal degradation of SDC4-syntenin. TSPN6 also inhibits the shedding of the SDC4 ectodomain, mimicking the effects of matrix metalloproteinase inhibitors. Taken together, our data identify TSPN6 as a regulator of the trafficking and processing of SDC4 and highlight an important physical and functional interconnection between these membrane scaffolds for the production of exosomes. These findings clarify our understanding of the molecular determinants governing EV formation and have potentially broad impact for EV-related biomedicine.

Effect of Matrix Metalloproteinase Inhibitor from Mulberry fruit extract on the Microtensile Bond Strength Stability: An in vitro Study

Objectives: The present in vitro study aimed to analyze the effect of two Mulberry fruit extracts on microtensile bond strength of an etch & rinse adhesive immediately and after thermocycling.Materials and Methods: Flat dentin surfaces of 30 sound human molars were bonded with an etch and rinse adhesive. Dentin surfaces were left untreated (control group) or were pretreated with either Morus alba water extract, Morus alba alcohol extract, Morus nigra water extract or Morus nigra alcohol extract. Nano-hybrid resin composite were incrementally built-up. The tooth/composite specimen was serially sectioned in order to produce beams of 0.9±0.1 mm in thickness. Each group was subdivided into two subgroups whether the teeth/composite specimens subjected to thermocycling or not. Each beam was individually fractured by a micro tensile testing machine. The data recorded in MPa, were tabulated and statistically analyzed.Results : Specimens treated with Morus alba and Morus nigra water extracts yielded significantly higher mean bond strengths than alcohol extracts in immediate micro-tensile bond values and after thermocycling. In addition ,Morus alba water extract revealed no statistically significant difference immediately and after thermocycling. Conclusion : Dentin pretreatment with Mulbery water extracts has no adverse effect on the immediate microtensile bond strength and it was able to maintain bond stability of adhesive to dentin.

Effects of matrix metalloproteinase inhibitors on N-methyl-D-aspartate receptor and contribute to long-term potentiation in the anterior cingulate cortex of adult mice

Matrix metalloproteinases (MMPs) have been suggested to contribute to long-term potentiation, behavioral learning, and memory. In the dorsal horn of spinal cord, MMPs were reported to contribute to injury-related changes, and inhibitors of MMPs have been proposed as potential analgesics. However, it is unclear whether MMP inhibitors produce these effects by inhibiting the function of N-methyl-D-aspartate receptor (NMDAR), a key receptor for the induction of long-term potentiation. In this study, we wanted to examine if MMP inhibitors affect NMDAR-mediated excitatory postsynaptic currents in the anterior cingulate cortex of adult mice. Among different subtype inhibitors we used, we found that MMP-9 and MMP-2/9 inhibitors did not change NMDAR-mediated excitatory postsynaptic currents. However, MMP-3 and broad-spectrum MMP inhibitors reduced the NMDAR-mediated excitatory postsynaptic currents. Consistently, MMP-9 and MMP-2/9 inhibitors had no effect on NMDAR-dependent long-term potentiation, but MMP-3 and broad-spectrum MMP inhibitors inhibited the induction of long-term potentiation. Our results suggest that MMP inhibitors may produce their effects by inhibiting NMDAR functions in central synapses.

Effect of matrix metalloproteinase inhibitor on disrupted E-cadherin after acid exposure in the human nasal epithelium.

Laryngopharyngeal reflux disease (LPRD) is one of potential factors in recalcitrant chronic rhinosinusitis with or without polyps. An increase in junctional permeability in the nasal mucosa in LPRD may be due to disrupted protein bridge formation with cell-to-cell adhesion molecules such as E-cadherin. Despite the relationship between nasal mucosal inflammation and LPRD, the clear mechanism by which acid reflux affects the nasal epithelium remains unclear. The expression levels and distribution patterns of E-cadherin in primary culture of nasal epithelial cells after acid exposure with or without dexamethasone and matrix metalloproteinase (MMP) inhibitor were determined using Western blot and immunocytochemistry. The functional roles of MMP inhibitor in maintaining junctional permeability in the nasal epithelium were elucidated by transepithelial permeability test. By acid exposure to nasal epithelial cells, mature E-cadherin was decreased and cleaved E-cadherin was increased. This was thought to be caused by cleavage of mature E-cadherin between cells and was confirmed by the increment of E-cadherin inside a cell in immunocytochemical evaluation. Whereas disruption of E-cadherin was not recovered by steroid medication with various treatments of dexamethasone, disrupted E-cadherin was restored to normal by inhibition of MMPs with actinonin, a broad MMP inhibitor. This recovery was functionally demonstrated by transepithelial permeability test. Our results suggest that altered expression of E-cadherin in the nasal epithelium by acid exposure may be a possible mechanism for nasal tissue injury in chronic nasal inflammation with LPRD, and that MMP inhibition is a potential treatment. NA. Laryngoscope, 128:E1-E7, 2018.

MMP inhibitor Ilomastat induced amoeboid-like motility via activation of the Rho signaling pathway in glioblastoma cells.

Matrix metalloproteinases (MMPs) play the important role in the process of glioblastoma cell invasion through 3D matrices. However, the effects of MMP inhibitors used in the treatment of malignant gliomas are unsatisfactory. The aim of this study was to explore the reason and mechanism by which cells move through the dense extracellular matrix without proteolysis. The results showed that MMP inhibitor (MMPI), Ilomastat, induced glioma cells to have an amoeboid-like morphology with invasive ability. Moreover, the RhoA/Rho kinase (ROCK)/myosin light chain (MLC) signal is involved in the MMPI-induced movement mode switch, and RhoA activation is dependent on P115RhoGEF. Importantly, combined inhibition of MMPs and ROCK enhanced the inhibition invasion function of MMPI and increased survival time in vitro and in vivo. The results suggested that glioma cells with MMPI treatment were able to compensate for the loss of invasive proteolysis-dependent migration capacity by acquiring an amoeboid-like migration mode and indicated that the combined MMP inhibitor and ROCK inhibitor can be used as an attractive antitumor drug candidate for the treatment of GBM.

Quantitative pre-clinical screening of therapeutics for joint diseases using contrast enhanced micro-computed tomography

The development of effective therapies for cartilage protection has been limited by a lack of efficient quantitative cartilage imaging modalities in pre-clinical invivo models. Our objectives were two-fold: first, to validate a new contrast-enhanced 3D imaging analysis technique, equilibrium partitioning of an ionic contrast agent-micro computed tomography (EPIC-μCT), in a rat medial meniscal transection (MMT) osteoarthritis (OA) model; and second, to quantitatively assess the sensitivity of EPIC-μCT to detect the effects of matrix metalloproteinase inhibitor (MMPi) therapy on cartilage degeneration. Rats underwent MMT surgery and tissues were harvested at 1, 2, and 3 weeks post-surgery or rats received an MMPi or vehicle treatment and tissues harvested 3 weeks post-surgery. Parameters of disease progression were evaluated using histopathology and EPIC-μCT. Correlations and power analyses were performed to compare the techniques. EPIC-μCT was shown to provide simultaneous 3D quantification of multiple parameters, including cartilage degeneration and osteophyte formation. In MMT animals treated with MMPi, OA progression was attenuated, as measured by 3D parameters such as lesion volume and osteophyte size. A post-hoc power analysis showed that 3D parameters for EPIC-μCT were more sensitive than 2D parameters requiring fewer animals to detect a therapeutic effect of MMPi. 2D parameters were comparable between EPIC-μCT and histopathology. This study demonstrated that EPIC-μCT has high sensitivity to provide 3D structural and compositional measurements of cartilage and bone in the joint. EPIC-μCT can be used in combination with histology to provide a comprehensive analysis to screen new potential therapies.

The role of matrix metalloproteinases in retinal pigment epithelial cell-induced gel contraction and collapse

Purpose: To determine the role of matrix metalloproteinases (MMP)-1, -2, and -9 in directing the behavior of human retinal pigment epithelial (HRPE) cells during contraction of three-dimensional collagen gels. Materials and Methods: The effect of HRPE cells on collagen gel invasion and contraction were quantified by using phase contrast microscopy. Immunohistochemistry of the gel using monoclonal antibodies against MMP-1, -2, and -9 was performed. The effects of MMP inhibitor, Batimastat (BB-94) on cultured HRPE cells, and gel contraction were observed. Results: HRPE cells mostly proliferated as sheets of cells on the surface of the collagen gel and only minimally invaded the gel. However, some HRPE cells were seen to invade the gel as single cells detaching from the surface sheets. Surface-located sheets of cells exerted a dose-dependent contraction on the gel and generally failed to express MMPs. Single cells invading the gel expressed MMP-2 and -9. No expression of MMP-1 was observed by HRPE cells. BB-94, at a dose of 500 nM and 5 μM, reduced the amount of gel contraction. Conclusions: These data indicate that MMPs are selectively involved in HRPE invasion and collagen gel contraction. Both these processes may be implicated in the pathogenesis of similar conditions in vivo in which contraction of collagen gel is a feature, for example, proliferative vitreoretinopathy.

Comparison of the Effects of Matrix Metalloproteinase Inhibitors on TNF-α Release from Activated Microglia and TNF-α Converting Enzyme Activity.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that regulate cell-matrix composition and are also involved in processing various bioactive molecules such as cell-surface receptors, chemokines, and cytokines. Our group recently reported that MMP-3, -8, and -9 are upregulated during microglial activation and play a role as proinflammatory mediators (Lee et al., 2010, 2014). In particular, we demonstrated that MMP-8 has tumor necrosis factor alpha (TNF-α)-converting enzyme (TACE) activity by cleaving the prodomain of TNF-α and that inhibition of MMP-8 inhibits TACE activity. The present study was undertaken to compare the effect of MMP-8 inhibitor (M8I) with those of inhibitors of other MMPs, such as MMP-3 (NNGH) or MMP-9 (M9I), in their regulation of TNF-α activity. We found that the MMP inhibitors suppressed TNF-α secretion from lipopolysaccharide (LPS)-stimulated BV2 microglial cells in an order of efficacy: M8I>NNGH>M9I. In addition, MMP inhibitors suppressed the activity of recombinant TACE protein in the same efficacy order as that of TNF-α inhibition (M8I>NNGH>M9I), proving a direct correlation between TACE activity and TNF-α secretion. A subsequent pro-TNF-α cleavage assay revealed that both MMP-3 and MMP-9 cleave a prodomain of TNF-α, suggesting that MMP-3 and MMP-9 also have TACE activity. However, the number and position of cleavage sites varied between MMP-3, -8, and -9. Collectively, the concurrent inhibition of MMP and TACE by NNGH, M8I, or M9I may contribute to their strong anti-inflammatory and neuroprotective effects.

Comparison of the Effects of Matrix Metalloproteinase Inhibitors on TNF-a Release from Activated Microglia and TNF-a Converting Enzyme Activity

Comparison of the Effects of Matrix Metalloproteinase Inhibitors on TNF-a Release from Activated Microglia and TNF-a Converting Enzyme Activity

Inhibition of Matrix Metalloproteinases (MMPs) as a Potential Strategy to Ameliorate Hypertension-Induced Cardiovascular Alterations

A group of proteases, the matrix metalloproteinases (MMPs) are well known for their capacity to degrade extracellular matrix (ECM) proteins. Particularly MMP-2 and MMP-9 contribute to the degradation and reorganization of the ECM components and are involved in the pathophysiology of cardiovascular remodeling. Imbalanced MMP activity promotes vascular smooth muscle cells and migration and proliferation and endothelial dysfunction, thus resulting in increased cardiovascular stiffness and hypertrophy. Furthermore, MMP-2 cleaves non-ECM protein substrates including cellular receptors and intracellular proteins, thus causing cardiac and vascular dysfunction. It is now becoming clear that increased MMP activity promotes long-lasting cardiovascular structural and functional alterations in both experimental and clinical hypertension, and this alteration may contribute to sustained hypertension and its complications. Other pathogenic mechanisms including activation of the renin-angiotensin-aldosterone system and oxidative stress activate and upregulate MMPs. Therefore, MMP inhibition may prevent the deleterious consequences of hypertension to the cardiovascular system. This review article will focus on growing evidence supporting the relevance of MMPs in hypertension and the effects of MMP inhibitors. Particularly, the effects of doxycycline used as a non selective MMP inhibitor in experimental and clinical studies will be discussed.

Imbalanced Matrix Metalloproteinases in Cardiovascular Complications of End‐Stage Kidney Disease: A Potential Pharmacological Target

End-stage kidney disease (ESKD) is a major health problem associated with very high morbidity and mortality secondary to cardiovascular complications, especially in ESKD patients on dialysis. Therefore, exploring key mechanisms underlying cardiovascular alterations associated with ESKD may offer reasonable pharmacological targets that may benefit these patients. Imbalanced matrix metalloproteinases (MMP) activities have been implicated in many cardiovascular diseases, and growing evidence now indicates that excessive MMP activities contribute to cardiovascular complications in ESKD patients. However, there is no study on the effects of MMP inhibitors (MMPIs) in such patients. MMPIs may prevent against the vascular and cardiac changes associated with ESKD. In this MiniReview, we aimed at reviewing current evidence supporting the idea that pharmacological inhibition of imbalanced MMP activities in ESKD may decrease the morbidity and mortality associated with cardiovascular complications in ESKD patients. However, MMPs have variable effects during different phases of kidney disease, and therefore optimal timing for MMP inhibition during a disease process may vary significantly and is largely undetermined. While current research shows that MMPs play a role in the pathogenesis of the cardiovascular alterations found in ESKD patients, clinical studies are required to validate the idea of using MMPIs in ESKD.

Experimental study on effects of matrix metalloproteinase inhibitor on posterior capsule opacification in rabbits

To determine whether matrix metalloproteinase (MMP) inhibitor can provide therapeutic effects for rabbits posterior capsule opacification in vivo and to observe the side effects of this drug on surrounding intraocular structures. Experimental research. New Zealand white rabbits were undertaken phacoemulsification operation. GM6001 at different concentrations (100, 200 and 500 µmol/L) and GM6001 negative control liqueur were infused into the capsule bags of the rabbits at the end of operation and two days after the operation. The incidence of posterior capsule opacification was assessed and the histological sections of posterior capsules were observed under microscope 12 weeks after the surgery. The anterior chamber response was observed on day 2 post-operatively. The changes of intraocular pressure were measured by day 2 and day 7. Corneal endothelial cells were observed under scanning electron microscope and iris, ciliary body and retina were observed under microscope on day 7. GM6001 significantly prevented posterior capsule opacification (P = 0.007). No opacification occurred on the rabbit posterior capsule in eyes with 200 and 500 µmol/L GM6001 on week 12 post-operatively in vivo. No cells were found on posterior capsule in 500 µmol/L group, whereas lens epithelial cells and fibroblasts were found in the controls under microscope. No difference of anterior chamber flare between the eyes with GM6001 at different concentrations and the control group (P = 0.380) by day 2 after the operation. The intraocular pressure in eyes with GM6001 was the same as that in the control 2-days (F = 0.642, P = 0.597) and 7-days (F = 0.179, P = 0.909) post-operation. The corneal endothelial cells in eyes with 500 µmol/L GM6001 arranged regularly and did not show any difference from that in the control eyes under scanning electron microscope 7-day after the operation. The iris, ciliary body and retina in eyes with 500 µmol/L GM6001 were normal in appearance 7-day after the operation. MMP inhibitor can prevent posterior capsule opacification effectively in rabbits in vivo and does not cause damage to surrounding intraocular structures, suggesting that MMP inhibitor may become a medication used for the prevention of lens posterior capsule opacification.

Matrix metalloproteinase inhibitors reduce collagen gel contraction and α‐smooth muscle actin expression by periodontal ligament cells

Orthodontic tooth movement requires remodeling of the periodontal tissues. The matrix metalloproteinases (MMPs) degrade the extracellular matrix components of the periodontal ligament, while the tissue inhibitors of metalloproteinases (TIMPs) control their activity. Synthetic MMP inhibitors have been developed to inhibit MMP activity. In this study, periodontal ligament cells in contracting collagen gels served as a model for enhanced periodontal remodeling. The effect of MMP inhibitors on gel contraction and on MMP and TIMP expression was analyzed. Human periodontal ligament cells were cultured in three-dimensional collagen gels and incubated with the MMP inhibitors BB94, CMT-3, doxycycline and Ilomastat. Gel contraction was determined using consecutive photographs. The relative amounts of MMPs and TIMPs were analyzed using substrate zymography and mRNA expression using quantitative polyermase chain reaction. All MMP inhibitors reduced MMP activity to about 20% of the control activity. They all reduced contraction, but CMT-3 and doxycycline had the strongest effect. These inhibitors also reduced MMP-2, MMP-3 and alpha-smooth muscle actin mRNA expression. The expression of MMP-1 mRNA seemed to be increased by CMT-3. No effects were found on the amounts of MMPs and TIMPs. Synthetic MMP inhibitors strongly reduced gel contraction by periodontal ligament cells. This was primarily caused by an inhibitory effect on MMP activity, which reduces matrix remodeling. In addition, alpha-smooth muscle actin expression was reduced by CMT-3 and doxycycline, which limits the contractile activity of the fibroblasts.

Study on inhibitory effects of matrix metalloproteinase inhibitor on migration of cultured human lens epithelial cells

To determine whether matrix metalloproteinases inhibitor can prevent human lens epithelial cell migration in lens capsule bag model from the donor eyes. This study was an experimental investigation. Sham cataract surgery were performed in 16 human donor eyes. The donor lens capsule bags were cultured and treated with a broad MMP inhibitor (GM6001) at different concentrations (1, 10 and 100 micromol/L) and without GM6001 (negative control). The distance of lens epithelial cells migration on the posterior capsule was measured in all capsule bags under microscope and total MMP-2 and MMP-9 protein production was determined by ELISA. The cell viability in all groups was determined using methylthiazol tetrazolium (MTT) test. Lens epithelial cells at the equator began to migrate by day 4. Epithelial cells migration onto the posterior capsule was significantly reduced by GM6001 in a dose dependent manner as compared with the controls (F = 53.79, P < 0.01). Seventy percent reduction (P < 0.01) and 98% reduction (P <0. 01) of migration were observed in 10 micromol/L and 100 micromol/L GM6001 treated cultures, respectively, as compared with that in control on day 20. MMP levels in capsular bag were reduced by GM6001, the greatest inhibitory effect was found at the highest concentrations of GM6001 (F = 86.59,72.96; P < 0.01). By day 20, the reduction in total MMP-2 level (P < 0.01) and MMP-9 level (P < 0.01) in 10 micromol/L GM6001 treated cultures was 70% as compared with that in control. Ninety percent reduction in MMP-2 level (P < 0.01) and 87% reduction in MMP-9 level (P < 0.01) were found in 100 micromol/L GM6001 treated cultures. Lens epithelial cells remained viable and proliferated in the presence of all concentrations of GM6001. No significant difference of cell viability between the controls and GM6001 treated cultures (1,10, and 100 micromol/L) was found by the MTT assay (F = 0.62, P > 0.05). MMP inhibitor inhibits the lens epithelial cell migration onto the posterior capsule and does not affect the cell viability in cultured lens capsule bags in vitro. Therefore, MMP inhibition may have a role in the treatment of posterior capsule opacification.