Matrix metalloproteinases regulate morphogenesis, migration and remodeling of epithelium, tongue skeletal muscle and cartilage in the mandibular arch

Development ◽  
1997 ◽  
Vol 124 (8) ◽  
pp. 1519-1530 ◽  
Author(s):  
J.R. Chin ◽  
Z. Werb
Keyword(s):  
Skeletal Muscle ◽  
Matrix Metalloproteinases ◽  
Paraxial Mesoderm ◽  
Gelatinase A ◽  
Meckel's Cartilage ◽  
Gelatinase B ◽  
Mandibular Arch ◽  
Meckel’S Cartilage ◽  
And Cartilage ◽  
Stromelysin 3

We have investigated the role of proteinases in the developmental program of bone, cartilage, tongue muscle and epithelial differentiation and remodeling in the mandibular arch during murine embryogenesis. Expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) was tissue-specific with little or no expression in the epithelium of tooth buds, tongue or oral cavity. Gelatinase A mRNA transcripts were strongly expressed in the perichondrium of Meckel's cartilage and mesenchymal areas of embryonic day 13–15 mandibles, whereas gelatinase B, collagenase-3, TIMP-1 and TIMP-2 mRNA were found primarily in the ossifying areas of the mandibles. The skeletal muscle of the tongue expressed stromelysin-3, TIMP-2 and TIMP-3 mRNA while stromelysin-3, TIMP-2 and gelatinase A were seen in the overlying connective tissue layer. Gelatinase A, gelatinase B, stromelysin-1, urokinase, TIMP-1 and TIMP-2 mRNA and protein activities were also detected in cultured mandibular explants. Culture of day 10 mandibular explants with a hydroxamic acid metalloproteinase inhibitor, but not with inhibitors of metalloendopeptidases (thiorphan and phosphoramidon), serine proteinases (aprotinin), cysteine proteinases (leupeptin) and urokinase (amiloride), altered mandibular morphogenesis dramatically. Development of the tongue (glossogenesis) and cartilage, but not bone or teeth was affected. Formation of the oral sulcus and fusion of the two epithelia of the medial sulcus were inhibited, and number and migration of myoblasts decreased. The resulting ‘tongue-tied phenotype’ indicates that MMPs are involved in epithelial morphogenesis and the migration of myoblasts to the region of the tongue. Development of the anterior segment of Meckel's cartilage was also inhibited and proteoglycan content of the cartilage was reduced by inhibiting MMPs. Our data suggest that matrix metalloproteinases play a pivotal role in the morphogenesis of structures derived from epithelium (oral sulcus), cranial paraxial mesoderm (tongue) and cranial neural crest (Meckel's cartilage).

scholarly journals Cell-mediated degradation of type IV collagen and gelatin films is dependent on the activation of matrix metalloproteinases

1992 ◽  
Vol 288 (2) ◽  
pp. 605-611 ◽  
Author(s):  
S J Atkinson ◽  
R V Ward ◽  
J J Reynolds ◽  
G Murphy
Keyword(s):  
Matrix Metalloproteinases ◽  
Oxygen Radicals ◽  
Type Iv Collagen ◽  
Model System ◽  
Dermal Fibroblasts ◽  
Gelatinase A ◽  
Reactive Oxygen Metabolite ◽  
Gelatinase B ◽  
Type Iv ◽  
Gelatin Films

The ability of normal rabbit dermal fibroblasts to degrade films of type IV collagen and gelatin when stimulated by phorbol ester was shown to be dependent on the induction, secretion and activation of 95 kDa gelatinase B and the secretion and activation of 72 kDa gelatinase A and stromelysin. Degradation was inhibited by exogenous human recombinant tissue inhibitor of metalloproteinases-1, specific antibodies to gelatinase and stromelysin and by the reactive-oxygen-metabolite inhibitor catalase. We discuss the various pathways for activation of matrix metalloproteinases in this model system and conclude that, although plasmin may play a key role in the activation of gelatinase B and stromelysin, gelatinase A is activated by a mechanism which has yet to be elucidated. The involvement of oxygen radicals in the direct activation of matrix metalloproteinases in this model is thought to be unlikely.

Memoirs: The Posterior End of Meckel's Cartilage and Related Ossifications in Bony Fishes

1937 ◽  
Vol s2-80 (317) ◽  
pp. 1-38
Author(s):  
R. WHEELER HAINES
Keyword(s):  
Joint Surface ◽  
Connective Tissues ◽  
Endochondral Bone ◽  
Meckel's Cartilage ◽  
Articular Process ◽  
Meckel’S Cartilage ◽  
Bony Fishes ◽  
Growth Zones ◽  
Special Growth ◽  
And Cartilage

1. In modern Dipnoi (Protopterus) the membrane bones are separated by connective tissue from Meekel's cartilage, and there is no endochondral or perichondral bone. The cartilage grows evenly over its whole extent. 2. In Polypterus a large articular ossifies the posterior end of the cartilage, including the retro-articular process, and spreads into the neighbouring connective tissues. 3. In Elops the joint surface is carried partly by the articular, and partly by the retro-articular, a special ossification of the retro-articular process. 4. In most teleosts (Mugil, Sardina, Trigla) the articular is absent and the angular invades the perichondrium and cartilage to form the joint surface. Special growth zones of flattened cells are formed in the cartilage which by their growth carry the retro-articular, angular, and dentary away from one another, stability of the jaw being maintained by new growth of the membranous parts of the bones. 5. Endochondral bone is reduced or absent in some specialized fishes (Tetrodon, Notopogon). 6. The sesamoid articular of teleosts is a separated part of the angular which gives insertion to the adductor mandibulae muscle. 7. An attempt is made to follow the evolution of Meckel's cartilage and the related ossifications by a comparison of the early Dipnoi, Crossopterygii, and Amphibia described in the literature with modern forms.

scholarly journals An Immunohistochemistry Study of Sox9, Runx2, and Osterix Expression in the Mandibular Cartilages of Newborn Mouse

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Hong Zhang ◽  
Xiaopeng Zhao ◽  
Zhiguang Zhang ◽  
Weiwei Chen ◽  
Xinli Zhang
Keyword(s):  
Hypertrophic Chondrocytes ◽  
Newborn Mouse ◽  
Late Development ◽  
Differentiation Process ◽  
Meckel's Cartilage ◽  
Meckel’S Cartilage ◽  
Hypertrophic Cell ◽  
Polymorphic Cell ◽  
And Cartilage ◽  
Cell Zone

The purpose of this study is to investigate the spacial expression pattern and functional significance of three key transcription factors related to bone and cartilage formation, namely, Sox9, Runx2, and Osterix in cartilages during the late development of mouse mandible. Immunohistochemical examinations of Sox9, Runx2, and Osterix were conducted in the mandibular cartilages of the 15 neonatal C57BL/6N mice. In secondary cartilages, both Sox9 and Runx2 were weakly expressed in the polymorphic cell zone, strongly expressed in the flattened cell zone and throughout the entire hypertrophic cell zone. Similarly, both transcriptional factors were weakly expressed in the uncalcified Meckel’s cartilage while strongly expressed in the rostral cartilage. Meanwhile, Osterix was at an extremely low level in cells of the flattened cell zone and the upper hypertrophic cell zone in secondary cartilages. Surprisingly, Osterix was intensely expressed in hypertrophic chondrocytes in the center of the uncalcified Meckel’s cartilage while moderately expressed in part of hypertrophic chondrocytes in the rostral process. Consequently, it is suggested that Sox9 is a main and unique positive regulator in the hypertrophic differentiation process of mandibular secondary cartilages, in addition to Runx2. Furthermore, Osterix is likely responsible for phenotypic conversion of Meckel’s chondrocytes during its degeneration.

An inverse correlation between expression of NCAM-A and the matrix-metalloproteinases gelatinase-A and gelatinase-B in human glioma cells in vitro

1997 ◽  
Vol 116 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Stephen L Maidment ◽  
Garry J Rucklidge ◽  
Harcharan K Rooprai ◽  
Geoffrey J Pilkington
Keyword(s):  
Matrix Metalloproteinases ◽  
Glioma Cells ◽  
Inverse Correlation ◽  
Gelatinase A ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Gelatinase B ◽  
The Matrix

scholarly journals Differential regulation of matrix metalloproteinases and their inhibitors in human glomerular epithelial cells in vitro.

1998 ◽  
Vol 9 (9) ◽  
pp. 1629-1637
Author(s):  
J Martin ◽  
R Steadman ◽  
J Knowlden ◽  
J Williams ◽  
M Davies
Keyword(s):  
Epithelial Cells ◽  
Matrix Metalloproteinases ◽  
Specific Inhibitor ◽  
Differential Regulation ◽  
Dependent Manner ◽  
Gelatinase A ◽  
Type Iv Collagenase ◽  
Gelatinase B ◽  
Type Iv ◽  
Glomerular Epithelial Cells

The present study examines the effect of transforming growth factor-beta1 (TGF-beta1) and interleukin-1beta (IL-1beta) on the regulation of gelatinase A, gelatinase B, tissue inhibitor of metalloproteinase-I (TIMP-I) and TIMP-II in human glomerular epithelial cells (GEC). The addition of TGF-beta1 resulted in the increased production and secretion of both gelatinase A (72-kD type IV collagenase) and gelatinase B (92-kD type IV collagenase), in a dose- and time-dependent manner. In contrast, the addition of IL-1beta to GEC resulted in the stimulation of secretion of gelatinase B but not gelatinase A. When the secretion of the regulatory inhibitors was examined, IL-1beta or TGF-beta1 both resulted in an increased secretion of TIMP-I, whereas the secretion of TIMP-II was downregulated. Such results demonstrate an independent and opposite regulation of the enzymes and their inhibitors. Of particular interest was the observation of the differential regulation of gelatinase A and its specific inhibitor TIMP-II (which binds to the latent form of this enzyme) in response to TGF-beta1. These results for the first time indicate that in human GEC, matrix metalloproteinases (MMP), as well as their specific inhibitors, are independently regulated by different cytokines. MMP and their regulatory tissue inhibitors (TIMP) play an important role in tissue remodeling. The results of the present study serve to emphasize both the complex regulation of matrix metabolism in the glomerulus and the potential pathologic role of an imbalance between the proteinases and their inhibitors in various forms of glomerular disease.

Human osteoblasts in culture synthesize collagenase and other matrix metalloproteinases in response to osteotropic hormones and cytokines

1992 ◽  
Vol 103 (4) ◽  
pp. 1093-1099 ◽  
Author(s):  
M.C. Meikle ◽  
S. Bord ◽  
R.M. Hembry ◽  
J. Compston ◽  
P.I. Croucher ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Matrix Metalloproteinases ◽  
Type I Collagen ◽  
Bone Cells ◽  
Type I ◽  
Gelatinase A ◽  
Human Osteoblasts ◽  
Gelatinase B ◽  
Collagen Substratum ◽  
Cells Cultured

Collagenase production by rodent osteoblasts in response to calciotropic hormones has led to the hypothesis that bone cells play a major role in bone resorption by degrading the surface osteoid layer, thereby exposing the underlying mineralized matrix to osteoclastic action. Many studies suggest, however, that this model might not apply to bone resorption in the human. Human osteoblasts have been shown to produce gelatinase-A (72 kDa) and TIMP-1 (tissue inhibitor of metalloproteinases), but previous investigators have been unable to demonstrate the synthesis of collagenase by human osteoblasts either constitutively or in response to bone resorptive agents. In the present study the ability of human osteoblasts to produce the matrix metalloproteinases (MMPs) collagenase, gelatinase and stromelysin, and their specific inhibitors TIMPs-1 and 2, was examined using highly sensitive and specific antisera and by zymography. Semi-quantitative histomorphometric data showed that cells cultured on either glass or a type I collagen substratum constitutively synthesized gelatinase-A and TIMP-1. On type I collagen, however, a small proportion of unstimulated cells produce both collagenase (7%) and gelatinase-B (95 kDa; 3%). Treatment of cells with either parathyroid hormone (PTH), 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3), or partially purified mononuclear cell conditioned medium (MCM), stimulated the synthesis of collagenase, gelatinase-B and stromelysin; MCM was 2- to 3-fold more potent than either PTH or 1,25(OH)2D3. Zymography using SDS/PAGE on conditioned media from cells cultured on type I collagen films revealed the presence of active gelatinase-A and that MCM stimulated progelatinase-B synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

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