Matrix metalloproteinases (MMPs) are a family of nine or more highly homologous Zn(++)-endopeptidases that collectively cleave most if not all of the constituents of the extracellular matrix. The present review discusses in detail the primary structures and the overlapping yet distinct substrate specificities of MMPs as well as the mode of activation of the unique MMP precursors. The regulation of MMP activity at the transcriptional level and at the extracellular level (precursor activation, inhibition of activated, mature enzymes) is also discussed. A final segment of the review details the current knowledge of the involvement of MMP in specific developmental or pathological conditions, including human periodontal diseases.

Matrix Metalloproteinases: A Review

Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels

It has long been appreciated that, for many types of cells, attachment to a substrate is required for their replication. Collagen substrates enhance the growth (64, 70, 109, 238) as well as the differentiation (40, 69, 85, 86, 146, 161, 184), of many cells in culture above that observed with other substrates such as plastic and glass. As discussed in this report, many cultured cells including fibroblasts, myoblasts, hepatocytes, chondrocytes, and certain epithelial cells are thought not to bind directly to the collagen substrate or to the plastic surface of culture dishes (31, 73, 74, 76, 77, 89, 93, 113, 164, 220) . Instead, extracellular glycoproteins bind the cells to the substrate. One of these attachment proteins, fibronectin, has been extensively studied (99, 151, 166, 227, 228, 244) . Fibronectin is produced by fibroblasts (13, 197, 246) and endothelial cells (102, 140) as well as some other cell types . It is also present in high concentrations in blood and serum (152) . In culture, serum fibronectin, as well as that produced by the cells, can bind to both the collagen substrates and the tissue culture plastic surface and mediate the attachment of cells (73, 113, 164, 242) . Circulating fibronectin participates in a variety of reactions important to wound healing, including the adhesion and spreading of platelets on collagen (10, 14, 75, 100, 204), binding to the fibrin clot (74, 150, 198) and to collagen (37, 46, 94, 103, 119), promoting opsonization reactions by phagocytic cells (18, 94, 201), and promoting fibroblast migration (6, 61) . Thus, fibronectin not only functions as an attachment protein, but also may play an important role in repair reactions . In the case of certain differentiated cells, such as chondrocytes (89) and epithelial cells (159, 220), glycoproteins different from fibronectin are active in attachment. The components of these extracellular matrices of fibroblasts, chondrocytes, and epithelial cells differ with the cell type, and they require separate attachment proteins to provide additional specificity to the interaction ofthe cell with its matrix. Alterations in cellsubstratum interactions are observed in differentiating cells and after spontaneous transformation of cells or exposure to oncogenic agents (99, 228) . This review will briefly outline our current knowledge of the types of collagen and their distribution and biosynthesis. Then, the interaction of cells with colREVIEW

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Role of collagenous matrices in the adhesion and growth of cells.

(First of Two Parts) COLLAGEN is the major macromolecule of most connective tissues, and it is widely believed that many human diseases, particularly chronic diseases, will be found to involve this protein either directly or indirectly. Since collagen biosynthesis was last reviewed in the Journal in 1972,1 much new information has been gained about the relatively complex pathway by which it is synthesized. We should like to consider this new information and some of its consequences in terms of the following questions: What is the structural information in the collagen molecule, and how does it determine the structure of the . . .

Biosynthesis of collagen and its disorders

Amniote phylogeny and the importance of fossils

Collagen moleculess with the chain comizposition [alpha1(III)](3), have been isolated from pepsin-solubilized collagen of dermis, aorta, and leiomlyoma of the uterus by differential salt precipitation. On denaturation, approximately 90 percent of this collagen is recovered as a gamma component (300,000 daltons). Reduction and alkylation of the high-molecular-weight component yields alpha1(III) chains (95,000 daltons). In addition to containing cysteine, alpha1(III) chains exhibit several other compositional differences when compared to alpha1(I), alpha1(II), or alpha2 chains from human tissues.

https://science.sciencemag.org/content/sci/183/4130/1200.full.pdf

Collagen Polymorphism: Characterization of Molecules with the Chain Composition [α1(III)]3 in Human Tissues

In recent years it has become evident that genetic polymorphism is dramatically expressed in the structural protein, collagen. Current information on the biochemical properties, biosynthesis, and tissue distribution of Type I, II, and III collagens is summarized with special reference to possible unique functional roles fulfilled by each of these collagens.

Biochemical characteristics and biological significance of the genetically-distinct collagens.

Isolation of three collagenous components of probable basement membrane origin from several tissues

Specific cleavage of the native Type III collagen molecule with trypsin: Similarity of the cleavage products to collagenase-produced fragments and primary structure at the cleavage site

Long-spacing-segment crystallites prepared from type III collagen with the chain composition [alpha1(III)]3 and type I collagen with the chain composition [alpha(I)]i12alpha2 have been compared in the electron microscope after positive. staining with phosphotungstic acid and uranyl acetate. The comparison revealed several differences in intensities of the cross-striation bands as well as significant differences in band positions. The latter occur most prominently in three distinct regions of the crystallites. Further, crystallites prepared from type III collagen contain an additional intensely staining band in an area corresponding to the carboxy-terminal end of the molecule. The latter band is still observed following limited pepsin digestion and presumably represents a slight elongation of the helical portion of the type III molecule when compared to the type I molecule. In spite of the somewhat altered distribution of charged groups as indicated in studies on the long-spacing-segment crystallites, type III molecules are capable of forming fibrils of the native type with a cross-striation pattern and periodicity virtually identical to that observed when type I molecules are precipitated as native fibers.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1975.tb03936.x

Edward J. Miller

Papers

Collagen Polymorphism: Characterization of Molecules with the Chain Composition [α1(III)]3 in Human Tissues

Biochemical characteristics and biological significance of the genetically-distinct collagens.

Isolation of three collagenous components of probable basement membrane origin from several tissues

Specific cleavage of the native Type III collagen molecule with trypsin: Similarity of the cleavage products to collagenase-produced fragments and primary structure at the cleavage site

Comparative electron-microscope studies on type-III and type-I collagens.