scholarly journals A Tale of Two Joints: The Role of Matrix Metalloproteases in Cartilage Biology

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Brandon J. Rose ◽  
David L. Kooyman
Keyword(s):  
Rheumatoid Arthritis ◽  
Extracellular Matrix ◽  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Embryonic Development ◽  
Tissue Remodeling ◽  
Matrix Metalloproteases ◽  
Extracellular Matrix Molecules ◽  
Cartilage Biology

Matrix metalloproteinases are a class of enzymes involved in the degradation of extracellular matrix molecules. While these molecules are exceptionally effective mediators of physiological tissue remodeling, as occurs in wound healing and during embryonic development, pathological upregulation has been implicated in many disease processes. As effectors and indicators of pathological states, matrix metalloproteinases are excellent candidates in the diagnosis and assessment of these diseases. The purpose of this review is to discuss matrix metalloproteinases as they pertain to cartilage health, both under physiological circumstances and in the instances of osteoarthritis and rheumatoid arthritis, and to discuss their utility as biomarkers in instances of the latter.

scholarly journals Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

2001 ◽  
Vol 12 (5) ◽  
pp. 373-398 ◽  
Author(s):  
Bjorn Steffensen ◽  
Lari Häkkinen ◽  
Hannu Larjava
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Wound Repair ◽  
Enzyme Activation ◽  
Processing Enzymes ◽  
The Matrix ◽  
Signaling Receptors ◽  
State Of Rest ◽  
And Function

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.

scholarly journals Transforming growth factor–β in tissue fibrosis

2020 ◽  
Vol 217 (3) ◽  
Author(s):  
Nikolaos G. Frangogiannis
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Cellular Targets ◽  
Extracellular Matrix Molecules ◽  
Interacting Networks

TGF-β is extensively implicated in the pathogenesis of fibrosis. In fibrotic lesions, spatially restricted generation of bioactive TGF-β from latent stores requires the cooperation of proteases, integrins, and specialized extracellular matrix molecules. Although fibroblasts are major targets of TGF-β, some fibrogenic actions may reflect activation of other cell types, including macrophages, epithelial cells, and vascular cells. TGF-β–driven fibrosis is mediated through Smad-dependent or non-Smad pathways and is modulated by coreceptors and by interacting networks. This review discusses the role of TGF-β in fibrosis, highlighting mechanisms of TGF-β activation and signaling, the cellular targets of TGF-β actions, and the challenges of therapeutic translation.

Molecular regulation of cellular invasion— role of gelatinase A and TIMP-2

1996 ◽  
Vol 74 (6) ◽  
pp. 823-831 ◽  
Author(s):  
Anita E. Yu ◽  
Robert E. Hewitt ◽  
David E. Kleiner ◽  
William G. Stetler-Stevenson
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Gelatinase A ◽  
Cellular Mechanisms ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
The Matrix ◽  
Cell Matrix Interactions

Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell–matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.Key words: tissue inhibitors of metalloproteinases, metalloproteinase, gelatinases, extracellular matrix, activation.

The Role of Dystroglycan and Its Ligands in Physiology and Disease

Physiology ◽  
2000 ◽  
Vol 15 (5) ◽  
pp. 255-259 ◽  
Author(s):  
Thomas Meier ◽  
Markus A. Ruegg
Keyword(s):  
Extracellular Matrix ◽  
Cell Membrane ◽  
Basement Membrane ◽  
Embryonic Development ◽  
Bacterial Pathogens ◽  
Membrane Integrity ◽  
Muscle Disease ◽  
Entry Point ◽  
Cell Membrane Integrity

Dystroglycan contributes to the formation of basement membrane during embryonic development and enforces cell membrane integrity by bridging cytoskeleton and components of the extracellular matrix. In several forms of muscle disease, dystroglycan is reduced in abundance. Moreover, human viral and bacterial pathogens use dystroglycan as their cellular entry point.

scholarly journals Role of Fibroblast Populations in Periodontal Wound Healing and Tissue Remodeling

2019 ◽  
Vol 10 ◽  
Author(s):  
Patricio C. Smith ◽  
Constanza Martínez ◽  
Jorge Martínez ◽  
Christopher A. McCulloch
Keyword(s):  
Wound Healing ◽  
Tissue Remodeling ◽  
Periodontal Wound Healing

Extracellular matrix 6: Role of matrix metalloproteinases in tumor invasion and metastasis

1993 ◽  
Vol 7 (15) ◽  
pp. 1434-1441 ◽  
Author(s):  
William G. Stetler‐Stevenson ◽  
Lance A. Liotta ◽  
David E. Kleiner
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Tumor Invasion ◽  
Invasion And Metastasis

scholarly journals The Role of Matrix Metalloproteinases in Diabetic Wound Healing in relation to Photobiomodulation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Sandra Matabi Ayuk ◽  
Heidi Abrahamse ◽  
Nicolette Nadene Houreld
Keyword(s):  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Main Function ◽  
Diabetic Wound ◽  
Impaired Wound Healing ◽  
Inflammatory Phase ◽  
Diabetic Wound Healing

The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs) play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM) during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing. The imbalance in MMPs may increase the chronicity of a wound, a familiar problem seen in diabetic patients. The association of diabetes with impaired wound healing and other vascular complications is a serious public health issue. These may eventually lead to chronic foot ulcers and amputation. Low intensity laser irradiation (LILI) or photobiomodulation (PBM) is known to stimulate several wound healing processes; however, its role in matrix proteins and diabetic wound healing has not been fully investigated. This review focuses on the role of MMPs in diabetic wound healing and their interaction in PBM.

scholarly journals Three-dimensional migration of macrophages requires Hck for podosome organization and extracellular matrix proteolysis

Blood ◽  
2010 ◽  
Vol 115 (7) ◽  
pp. 1444-1452 ◽  
Author(s):  
Céline Cougoule ◽  
Véronique Le Cabec ◽  
Renaud Poincloux ◽  
Talal Al Saati ◽  
Jean-Louis Mège ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Spatial Organization ◽  
Ectopic Expression ◽  
Three Dimensional ◽  
Matrix Metalloproteases ◽  
3 Dimensional ◽  
Normal Expression ◽  
Migration Of Macrophages

Abstract Tissue infiltration of phagocytes exacerbates several human pathologies including chronic inflammations or cancers. However, the mechanisms involved in macrophage migration through interstitial tissues are poorly understood. We investigated the role of Hck, a Src-family kinase involved in the organization of matrix adhesion and degradation structures called podosomes. In Hck−/− mice submitted to peritonitis, we found that macrophages accumulated in interstitial tissues and barely reached the peritoneal cavity. In vitro, 3-dimensional (3D) migration and matrix degradation abilities, 2 protease-dependent properties of bone marrow–derived macrophages (BMDMs), were affected in Hck−/− BMDMs. These macrophages formed few and undersized podosome rosettes and, consequently, had reduced matrix proteolysis operating underneath despite normal expression and activity of matrix metalloproteases. Finally, in fibroblasts unable to infiltrate matrix, ectopic expression of Hck provided the gain–of–3D migration function, which correlated positively with formation of podosome rosettes. In conclusion, spatial organization of podosomes as large rosettes, proteolytic degradation of extracellular matrix, and 3D migration appeared to be functionally linked and regulated by Hck in macrophages. Hck, as the first protein combining a phagocyte-limited expression with a role in 3D migration, could be a target for new anti-inflammatory and antitumor molecules.

Sign in / Sign up

Export Citation Format

Share Document