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MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 April 2022) | Viewed by 40954

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Special Issue Editor

Dr. Eric Huet

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Guest Editor

TRePCa—Therapeutic Resistance in Prostate Cancer, Univ Paris Est Creteil, F-94010 Creteil, France
Interests: matrix biology; tumor microenvironment, matric metalloproteinases; extracellular vesicles; cancer-associated fibroblast; EMMPRIN
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

MMPs have been implicated in numerous physiological and pathological situations, such as neoplasia, osteogenesis, myocardial infarction, osteoarthritis, or inflammation. Wide-ranging evidence has also implicated MMP dysregulation in tumor invasion, neoangiogenesis, and metastasis. EMMPRIN, a membrane glycoprotein greatly enriched on the surface of tumor cells, has been shown to stimulate the synthesis of MMPs in stromal cells and may account for the increased MMP expression in most cancer tissues. Apart from direct cell contact, cell interactions can also be influenced by soluble factors such as cytokines, growth factors, or extracellular vesicles. Such nodes of communication between cells might lead to dysregulations of ECM remodeling in physiological and pathological processes. In this Special Issue, original and review articles on basic science and preclinical and clinical findings are warmly welcome to contribute to our understanding of MMPs and their regulations.

Dr. Eric Huet
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Matrix metalloproteinases
EMMPRIN
Tissue remodeling
Cell interactions
Physiopathology

Published Papers (13 papers)

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Research

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18 pages, 40073 KiB

Open AccessArticle

Generation of Matrix Degradation Products Using an In Vitro MMP Cleavage Assay

by Niklas Wagner, Anna E. Rapp, Sebastian Braun, Markus Ehnert, Thomas Imhof, Manuel Koch, Zsuzsa Jenei-Lanzl, Frank Zaucke and Andrea Meurer

Int. J. Mol. Sci. 2022, 23(11), 6245; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116245 - 02 Jun 2022

Cited by 2 | Viewed by 2254

Abstract

Matrix metalloproteinases (MMPs) play crucial roles in tissue homeostasis and pathologies by remodeling the extracellular matrix. Previous studies have demonstrated the biological activities of MMP-derived cleavage products. Furthermore, specific fragments can serve as biomarkers. Therefore, an in vitro cleavage assay to identify substrates and characterize cleavage patterns could provide important insight in disease-relevant mechanisms and the identification of novel biomarkers. In the pathogenesis of osteoarthritis (OA), MMP-2, -8, -9 and -13 are of vital importance. However, it is unclear which protease can cleave which matrix component. To address this question, we established an in vitro cleavage assay using recombinantly expressed MMPs and the two cartilage matrix components, COMP and thrombospondin-4. We found a time- and concentration-dependent degradation and an MMP-specific cleavage pattern for both proteins. Cleavage products can now be enriched and purified to investigate their biological activity. To verify the in vivo relevance, we compared the in vitro cleavage patterns with serum and synovial fluid from OA patients and could indeed detect fragments of similar size in the human samples. The cleavage assay can be adapted to other MMPs and substrates, making it a valuable tool for many research fields. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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13 pages, 2669 KiB

Open AccessArticle

Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma

by Mirjami Kaasinen, Jaana Hagström, Harri Mustonen, Timo Sorsa, Malin Sund, Caj Haglund and Hanna Seppänen

Int. J. Mol. Sci. 2022, 23(6), 3314; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063314 - 18 Mar 2022

Cited by 4 | Viewed by 1779

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related death globally, and, despite improvements in diagnostics and treatment, survival remains poor. Matrix metalloproteinases (MMPs) are enzymes involved in stroma remodelling in inflammation and cancer. MMP-8 plays a varied prognostic role in cancers of the gastrointestinal tract. We examined the prognostic value of MMP-8 immunoexpression in tumour tissue and the amount of MMP-8-positive polymorphonuclear cells (PMNs) in PDAC and their association with immune responses using C-reactive protein (CRP) as a marker of systemic inflammation. Tumour samples from 141 PDAC patients undergoing surgery in 2002–2011 at the Department of Surgery, Helsinki University Hospital were stained immunohistochemically, for which we evaluated MMP-8 expression in cancer cells and the amount of MMP-8-positive PMNs. We assessed survival using the Kaplan–Meier analysis while uni- and multivariable analyses relied on the Cox proportional hazards model. A negative MMP-8 stain and elevated CRP level predicted a poor prognosis (hazard ratio [HR] = 6.95; 95% confidence interval (CI) 2.69–17.93; p < 0.001) compared to a positive stain and low CRP level (<10 mg/L). The absence of PMNs together with an elevated CRP level also predicted an unfavourable outcome (HR = 3.17; 95% CI 1.60–6.30; p = 0.001). MMP-8 expression in the tumour served as an independent positive prognostic factor (HR = 0.33; 95% CI 0.16–0.68; p = 0.003). Tumour MMP-8 expression and a low CRP level may predict a favourable outcome in PDAC with similar results for MMP-8-positive PMNs and low CRP levels. Tumoural MMP-8 expression represents an independent positive prognostic factor in PDAC. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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11 pages, 1814 KiB

Open AccessArticle

Salidroside, 8(E)-Nuezhenide, and Ligustroside from Ligustrum japonicum Fructus Inhibit Expressions of MMP-2 and -9 in HT 1080 Fibrosarcoma

by Hojun Kim, Chang-Suk Kong and Youngwan Seo

Int. J. Mol. Sci. 2022, 23(5), 2660; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052660 - 28 Feb 2022

Cited by 4 | Viewed by 1756

Abstract

A phenyl ethanoid, salidroside (SAL), and two secoiridoids, 8(E)-nuezhenide (NZD) and ligustroside (LIG), were isolated from fruits of Ligustrumjaponicum, used as traditional folk medicine, and their chemical structures were elucidated by the comparison of spectral data with published literature. Matrix metalloproteinases (MMPs) are major enzymes that play crucial roles in the metastasis and invasive behavior of tumors. In particular, MMP-2 and MMP-9, regulated by the MAPK signaling pathways, including p38, ERK and JNK, are known to play a key role in the degradation of the basement membrane. In the present study, the effects of SAL, NZD and LIG on the expression of MMP-2 and -9 were examined in phorbol 12-myristate 13-acetate (PMA)-induced HT 1080 cells. All the compounds significantly lowered the amount of MMP-2 and MMP-9 released, as determined by gelatin zymography and ELISA. In addition, the mRNA and protein expression levels of MMP-2 and MMP-9 were significantly suppressed, as measured by RT-PCR and Western blotting. According to the Western blotting assay, SAL and LIG effectively reduced the expression of MMP-2 in a dose-dependent manner. NZD lowered the expression of MMP-9 in a similar way. The phosphorylation of p38, ERK and JNK was also significantly suppressed by these compounds. These findings suggest that all the compounds regulate the release and expression of MMP-2 and MMP-9 via MAPK signaling pathways. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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14 pages, 5417 KiB

Open AccessArticle

Doxycycline Decreases Atherosclerotic Lesions in the Aorta of ApoE^-⁄- and Ovariectomized Mice with Correlation to Reduced MMP-2 Activity

by Keuri E. Rodrigues, Aline Azevedo, Pricila R. Gonçalves, Maria H. B. Pontes, Gustavo M. Alves, Ruan R. Oliveira, Cristine B. Amarante, João P. M. Issa, Raquel F. Gerlach and Alejandro F. Prado

Int. J. Mol. Sci. 2022, 23(5), 2532; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052532 - 25 Feb 2022

Cited by 3 | Viewed by 2490

Abstract

Atherogenic events promote changes in vessel walls, with alteration of the redox state, and increased activity of matrix metalloproteinases (MMPs). Thus, this study aims to evaluate aortic remodeling, MMP activity, and reactive oxygen species (ROS) levels after treatment with doxycycline in ApoE^-⁄- and ovariectomized mice (OVX). Female ApoE^-⁄--knockout mice (5 weeks) were submitted to ovariectomy surgery to induce experimental menopause. They then received chow enriched with 1% cholesterol to induce hypercholesterolemia. The animals were divided into two experimental groups: ApoE^-⁄-/OVX vehicle and ApoE^-⁄-/OVX doxycycline (30 mg/kg) administered by gavage once a day for 28 days (15th to the 18th week of life). Blood samples were collected to measure total cholesterol and fractions. The aorta was used for morphometry and to measure the activity and expression of MMP-2 and ROS levels. The ApoE^-⁄-/OVX doxycycline group showed no change in total and fraction cholesterol levels. However, there was a reduction in ROS levels, MMP-2 expression, and activity that correlated with a decrease in atherosclerotic lesions relative to the ApoE^-⁄-/OVX vehicle (p > 0.05). Therefore, we conclude that doxycycline in ApoE^-⁄-/OVX animals promotes a reduction in atherosclerotic lesions by reducing ROS and MMP-2 activity and expression. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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21 pages, 5262 KiB

Open AccessArticle

Anti-Inflammatory Effects of Rhamnetin on Bradykinin-Induced Matrix Metalloproteinase-9 Expression and Cell Migration in Rat Brain Astrocytes

by Chien-Chung Yang, Li-Der Hsiao, Ya-Fang Shih, Zih-Yao Yu and Chuen-Mao Yang

Int. J. Mol. Sci. 2022, 23(2), 609; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020609 - 06 Jan 2022

Cited by 3 | Viewed by 1854

Abstract

Bradykinin (BK) has been shown to induce matrix metalloproteinase (MMP)-9 expression and participate in neuroinflammation. The BK/MMP-9 axis can be a target for managing neuroinflammation. Our previous reports have indicated that reactive oxygen species (ROS)-mediated nuclear factor-kappaB (NF-κB) activity is involved in BK-induced MMP-9 expression in rat brain astrocytes (RBA-1). Rhamnetin (RNT), a flavonoid compound, possesses antioxidant and anti-inflammatory effects. Thus, we proposed RNT could attenuate BK-induced response in RBA-1. This study aims to approach mechanisms underlying RNT regulating BK-stimulated MMP-9 expression, especially ROS and NF-κB. We used pharmacological inhibitors and siRNAs to dissect molecular mechanisms. Western blotting and gelatin zymography were used to evaluate protein and MMP-9 expression. Real-time PCR was used for gene expression. Wound healing assay was applied for cell migration. 2ʹ,7ʹ-dichlorodihydrofluorescein diacetate (H2DCF-DA) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) were used for ROS generation and NOX activity, respectively. Promoter luciferase assay and chromatin immunoprecipitation (ChIP) assay were applied to detect gene transcription. Our results showed that RNT inhibits BK-induced MMP-9 protein and mRNA expression, promoter activity, and cell migration in RBA-1 cells. Besides, the levels of phospho-PKCδ, NOX activity, ROS, phospho-ERK1/2, phospho-p65, and NF-κB p65 binding to MMP-9 promoter were attenuated by RNT. In summary, RNT attenuates BK-enhanced MMP-9 upregulation through inhibiting PKCδ/NOX/ROS/ERK1/2-dependent NF-κB activity in RBA-1. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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15 pages, 4116 KiB

Open AccessArticle

Homophilic Interaction of CD147 Promotes IL-6-Mediated Cholangiocarcinoma Invasion via the NF-κB-Dependent Pathway

by Paweena Dana, Ryusho Kariya, Worachart Lert-itthiporn, Wunchana Seubwai, Saowaluk Saisomboon, Chaisiri Wongkham, Seiji Okada, Sopit Wongkham and Kulthida Vaeteewoottacharn

Int. J. Mol. Sci. 2021, 22(24), 13496; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413496 - 16 Dec 2021

Cited by 10 | Viewed by 2205

Abstract

Cholangiocarcinoma (CCA), an aggressive cancer of bile ducts, is a well-known chronic inflammation-related disease. The major impediment in CCA treatment is limited treatment options for advanced disease; hence, an alternative is urgently required. The role of CD147 on cytokine production has been observed in inflammation-related diseases, but not in CCA. Therefore, this study was focused on CD147-promoting proinflammatory cytokine production and functions. Proinflammatory cytokine profiles were compared between CD147 expressing CCA cells and CD147 knockout cells (CD147 KO). Three cytokines, namely interleukin (IL)-6, IL-8, and granulocyte–monocyte colony-stimulating factor (GM-CSF), were dramatically diminished in CD147 KO clones. The involvement of the CD147-related cytokines in CCA invasion was established. CD147-promoted IL-6, IL-8, and GM-CSF secretions were regulated by NF-κB nuclear translocation, Akt activation, and p38 phosphorylation. CD147-fostering IL-6 production was dependent on soluble CD147, CD147 homophilic interaction, and NF-κB function. The overexpression of specific genes in CCA tissues compared to normal counterparts emphasized the clinical importance of these molecules. Altogether, CD147-potentiated proinflammatory cytokine production leading to CCA cell invasion is shown for the first time in the current study. This suggests that modulation of CD147-related inflammation might be a promising choice for advanced CCA treatment. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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25 pages, 8602 KiB

Open AccessArticle

Design and Synthesis of Water-Soluble and Potent MMP-13 Inhibitors with Activity in Human Osteosarcoma Cells

by Jose Maria Zapico, Lourdes Acosta, Miryam Pastor, Loganathan Rangasamy, Laura Marquez-Cantudo, Claire Coderch, Irene Ortin, Maria Nicolau-Sanus, Leonor Puchades-Carrasco, Antonio Pineda-Lucena, Alejandro Majali-Martinez, Pilar Ramos, Beatriz de Pascual-Teresa and Ana Ramos

Int. J. Mol. Sci. 2021, 22(18), 9976; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189976 - 15 Sep 2021

Cited by 5 | Viewed by 3044

Abstract

Osteoarthritis is a degenerative disease, often resulting in chronic joint pain and commonly affecting elderly people. Current treatments with anti-inflammatory drugs are palliative, making the discovery of new treatments necessary. The inhibition of matrix metalloproteinase MMP-13 is a validated strategy to prevent the progression of this common joint disorder. We recently described polybrominated benzotriazole derivatives with nanomolar inhibitory activity and a promising selectivity profile against this collagenase. In this work, we have extended the study in order to explore the influence of bromine atoms and the nature of the S1′ heterocyclic interacting moiety on the solubility/selectivity balance of this type of compound. Drug target interactions have been assessed through a combination of molecular modeling studies and NMR experiments. Compound 9a has been identified as a water-soluble and highly potent inhibitor with activity in MG-63 human osteosarcoma cells. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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Review

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25 pages, 1093 KiB

Open AccessReview

The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview

by Giovanni Barillari, Ombretta Melaiu, Marco Gargari, Silvia Pomella, Roberto Bei and Vincenzo Campanella

Int. J. Mol. Sci. 2022, 23(15), 8336; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158336 - 28 Jul 2022

Cited by 5 | Viewed by 2682

Abstract

Cluster of differentiation (CD)147, also termed extracellular matrix metalloprotease inducer or basigin, is a glycoprotein ubiquitously expressed throughout the human body, the oral cavity included. CD147 actively participates in physiological tissue development or growth and has important roles in reactive processes such as inflammation, immunity, and tissue repair. It is worth noting that deregulated expression and/or activity of CD147 is observed in chronic inflammatory or degenerative diseases, as well as in neoplasms. Among the latter, oral squamous cell carcinoma (OSCC) is characterized by an upregulation of CD147 in both the neoplastic and normal cells constituting the tumor mass. Most interestingly, the expression and/or activity of CD147 gradually increase as healthy oral mucosa becomes inflamed; hyperplastic/dysplastic lesions are then set on, and, eventually, OSCC develops. Based on these findings, here we summarize published studies which evaluate whether CD147 could be employed as a marker to monitor OSCC development and progression. Moreover, we describe CD147-promoted cellular and molecular events which are relevant to oral carcinogenesis, with the aim to provide useful information for assessing whether CD147 may be the target of novel therapeutic approaches directed against OSCC. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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33 pages, 1730 KiB

Open AccessReview

Matrix Metalloproteinases and Their Inhibitors in Pulmonary Fibrosis: EMMPRIN/CD147 Comes into Play

by Lourdes Chuliá-Peris, Cristina Carreres-Rey, Marta Gabasa, Jordi Alcaraz, Julián Carretero and Javier Pereda

Int. J. Mol. Sci. 2022, 23(13), 6894; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23136894 - 21 Jun 2022

Cited by 32 | Viewed by 5112

Abstract

Pulmonary fibrosis (PF) is characterized by aberrant extracellular matrix (ECM) deposition, activation of fibroblasts to myofibroblasts and parenchymal disorganization, which have an impact on the biomechanical traits of the lung. In this context, the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) is lost. Interestingly, several MMPs are overexpressed during PF and exhibit a clear profibrotic role (MMP-2, -3, -8, -11, -12 and -28), but a few are antifibrotic (MMP-19), have both profibrotic and antifibrotic capacity (MMP7), or execute an unclear (MMP-1, -9, -10, -13, -14) or unknown function. TIMPs are also overexpressed in PF; hence, the modulation and function of MMPs and TIMP are more complex than expected. EMMPRIN/CD147 (also known as basigin) is a transmembrane glycoprotein from the immunoglobulin superfamily (IgSF) that was first described to induce MMP activity in fibroblasts. It also interacts with other molecules to execute non-related MMP aactions well-described in cancer progression, migration, and invasion. Emerging evidence strongly suggests that CD147 plays a key role in PF not only by MMP induction but also by stimulating fibroblast myofibroblast transition. In this review, we study the structure and function of MMPs, TIMPs and CD147 in PF and their complex crosstalk between them. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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29 pages, 1306 KiB

Open AccessReview

The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms

by Miłosz Caban, Katarzyna Owczarek and Urszula Lewandowska

Int. J. Mol. Sci. 2022, 23(8), 4256; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084256 - 12 Apr 2022

Cited by 17 | Viewed by 3644

Abstract

Eye diseases are associated with visual impairment, reduced quality of life, and may even lead to vision loss. The efficacy of available treatment of eye diseases is not satisfactory. The unique environment of the eye related to anatomical and physiological barriers and constraints limits the bioavailability of existing agents. In turn, complex ethiopathogenesis of ocular disorders that used drugs generally are non-disease specific and do not act causally. Therefore, there is a need for the development of a new therapeutic and preventive approach. It seems that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have a significant role in the development and progression of eye diseases and could be used in the therapy of these disorders as pharmacological targets. MMPs and TIMPs play an important role in the angiogenesis, epithelial-mesenchymal transition, cell invasion, and migration, which occur in ocular diseases. In this review, we aim to describe the participation of MMPs and TIMPs in the eye diseases, such as age-related macular degeneration, cataract, diabetic retinopathy, dry eye syndrome, glaucoma, and ocular cancers, posterior capsule opacification focusing on potential mechanisms. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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18 pages, 1051 KiB

Open AccessReview

The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes

by Ionut Luchian, Ancuta Goriuc, Darius Sandu and Mihai Covasa

Int. J. Mol. Sci. 2022, 23(3), 1806; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031806 - 04 Feb 2022

Cited by 76 | Viewed by 7141

Abstract

Severe periodontitis, a destructive inflammatory disease of the supporting tissues of the teeth, ranks sixth in terms of global spread, affecting about 11% of the population. Metalloproteinases (MMPs) are extracellular matrix (ECM) macromolecules that are important in cellular development and morphogenesis, and they are capable of activating growth factors in their proximity, cell surface receptors, and adhesion molecules. MMPs are part of a major family of zinc-dependent endopeptidases, and their activity is modulated and regulated by certain inhibitors known as tissue metalloproteinase inhibitors (TIMPs). Because type I collagen is the major component of the periodontal extracellular matrix, special attention has been paid to the role of collagenases, especially MMP-8 and MMP-13 and gelatinases, MMP-2 and MMP-9, in periodontal diseases. In fact, MMP-8 (or collagenase 2) is currently one of the most promising biomarkers for periodontitis in oral fluids. Among them, salivary MMP-9 has been shown to be a more sensitive marker for periodontal inflammation during orthodontic treatment, which opens new perspectives in reducing periodontal hazards during such treatments. Both MMP-8 and MMP-9 are extremely valuable diagnostic tools in treating periodontitis, and future studies and healthcare policies should focus on implementing more accessible methods of chairside testing in order to reduce the prevalence of this disease. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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13 pages, 26079 KiB

Open AccessReview

Metalloproteinases in Endometrial Cancer—Are They Worth Measuring?

by Kaja Michalczyk and Aneta Cymbaluk-Płoska

Int. J. Mol. Sci. 2021, 22(22), 12472; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212472 - 19 Nov 2021

Cited by 3 | Viewed by 2021

Abstract

Endometrial cancer is one of the most common gynecological malignancies, yet the molecular mechanisms that lead to tumor development and progression are still not fully established. Matrix metalloproteinases (MMPs) are a group of enzymes that play an important role in carcinogenesis. They are proteases involved in the degradation of the extracellular matrix (ECM) that surrounds the tumor and the affected tissue allows cell detachment from the primary tumor causing local invasion and metastasis formation. Recent investigations demonstrate significantly increased metalloproteinase and metalloproteinase inhibitor levels in patients with endometrial cancer compared to those with normal endometrium. In this review, we aim to show their clinical significance and possible use in the diagnosis and treatment of patients with endometrial cancer. We have critically summarized and reviewed the research on the role of MMPs in endometrial cancer. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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27 pages, 972 KiB

Open AccessReview

MMPs and TIMPs Expression Levels in the Periodontal Ligament during Orthodontic Tooth Movement: A Systematic Review of In Vitro and In Vivo Studies

by Christian Behm, Michael Nemec, Fabian Weissinger, Marco Aoqi Rausch, Oleh Andrukhov and Erwin Jonke

Int. J. Mol. Sci. 2021, 22(13), 6967; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136967 - 28 Jun 2021

Cited by 16 | Viewed by 3346

Abstract

Background: During orthodontic tooth movement (OTM), applied orthodontic forces cause an extensive remodeling of the extracellular matrix (ECM) in the periodontal ligament (PDL). This is mainly orchestrated by different types of matrix metalloproteinases (MMPs) and their tissue inhibitors of matrix metalloproteinases (TIMPs), which are both secreted by periodontal ligament (PDL) fibroblasts. Multiple in vitro and in vivo studies already investigated the influence of applied orthodontic forces on the expression of MMPs and TIMPs. The aim of this systematic review was to explore the expression levels of MMPs and TIMPs during OTM and the influence of specific orthodontic force-related parameters. Methods: Electronic article search was performed on PubMed and Web of Science until 31 January 2021. Screenings of titles, abstracts and full texts were performed according to PRISMA, whereas eligibility criteria were defined for in vitro and in vivo studies, respectively, according to the PICO schema. Risk of bias assessment for in vitro studies was verified by specific methodological and reporting criteria. For in vivo studies, risk of bias assessment was adapted from the Joanna Briggs Institute Critical Appraisal Checklist for analytical cross-sectional study. Results: Electronic article search identified 3266 records, from which 28 in vitro and 12 in vivo studies were included. The studies showed that orthodontic forces mainly caused increased MMPs and TIMPs expression levels, whereas the exact effect may depend on various intervention and sample parameters and subject characteristics. Conclusion: This systematic review revealed that orthodontic forces induce a significant effect on MMPs and TIMPs in the PDL. This connection may contribute to the controlled depletion and formation of the PDLs’ ECM at the compression and tension site, respectively, and finally to the highly regulated OTM. Full article

(This article belongs to the Special Issue MMPs and EMMPRIN/CD147 in Physiological and Pathological Processes)

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