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At least 19 recordsLinked to original sources

Plasminogen activators and plasminogen activator inhibitors in connective tissues and connective tissue cells: influence of the neuropeptide substance P on expression.

Tissue segments isolated from ligament, epiligament, and synovial tissues from mature female New Zealand White Rabbits were demonstrated to constitutively secrete a plasminogen activator. Several tissues were also observed to constitutively secrete a plasminogen activator inhibitor which was detected in the form of a PA-PAI complex. Heterogeneity was observed in PA and PAI activity between the different connective tissues. Heterogeneity also existed between and within the medial collateral (MCL), lateral collateral (LCL), and the anterior cruciate (ACL) ligaments. In addition to the differences in constitutive expression of PA and PAI activity, differences in the responsiveness to the neuropeptide substance P (10(-5)-10(-9) M) were also detected. This responsiveness to substance P was displayed by an increase in PA and PAI activity in the conditioned medium. The pattern of responsiveness reflected the degree of innervation of these tissues. That is, synovium and epiligament tissue were the most responsive tissues to substance P while the MCL, LCL and ACL were less responsive to the neuropeptide. Parallel results were obtained using cell culture with fibroblasts isolated from the above mentioned tissues. That is, the pattern of responsiveness was similar between cells and tissue segments. More specifically, cells isolated from both synovium and epiligament increased their both their PA (slightly) and PAI activity following exposure to substance P. This was demonstrated at both the protein and RNA level. Thus, cells within a tissue maintain their phenotype when removed from their three-dimensional matrix. These results are unique in demonstrating that normal ligament and synovial cells and tissue respond to substance P by altering the expression of PA and PAI activity. This investigation further supports the concept that innervation may be important in normal connective tissue function.

Animals↗

Periodontal connective tissue.

Connective tissues of the periodontium are composed of cells and their related extracellular matrix components. For these tissues to respond appropriately during development and regeneration as well as in health, a precise regulation of cell-cell interactions and cell-substrata interactions must occur. Thus, in order to achieve more predictable clinical results, it is critical that the mechanisms and proteins and factors guiding tissue development, maintenance, and regeneration be understood at the cellular and molecular level. This has resulted in an increased emphasis on identifying components of the periodontium and subsequently determining how these proteins and factors regulate cell behavior. This review summarizes our current knowledge of the proteins and factors considered important to development, maintenance, and regeneration of periodontal tissues.

Cell Adhesion Molecules↗

Localization of connective tissue growth factor in human uterine tissues.

Connective tissue growth factor (CTGF) is a recently described heparin-binding mitogen for fibroblasts and smooth muscle cells. The aim of this study was to investigate the production of CTGF by human uterine tissues using immunohistochemical and Northern blotting analyses. For immunohistochemistry, formalin-fixed human proliferative (n = 5), early secretory (n = 5; days 15-19), mid-secretory (n = 5; days 20-23), late secretory (n = 5; days 24-28) endometrial, and decidual (n = 5) tissues were stained using a highly specific affinity-purified polyclonal antibody raised against residues 81-94 of human CTGF. Myometrial (n = 5) and leiomyoma (n = 5) tissues were also used for CTGF immunochemistry. In proliferative endometrium, epithelial and vascular endothelial cells showed strong CTGF immunoreactivity, whereas stromal cells were negative or only weakly positive for the CTGF protein. Throughout the entire secretory stage, CTGF was detected in epithelial and endothelial cells of endometrium. Stromal cells showed strong immunoreactivity to CTGF only in oedematous areas for early and mid-secretory endometrium, and in decidualized regions of late secretory endometrium. During pregnancy, the decidual, epithelial and endothelial cells of the endometrium were all immunoreactive to CTGF. In myometrial and leiomyoma samples, CTGF immunoreactivity was found only in the endothelial cells. Northern blotting of mRNA from normal uterus (n = 2) or leiomyoma (n = 6) using a 320 bp human CTGF cDNA probe revealed a single 2.4 kb transcript. This study is the first to demonstrate CTGF gene expression and localization of its encoded protein in human uterine tissues. The cell- and cycle-specific localization of CTGF support a role for this molecule in regulating aspects of uterine cell growth, migration, and/or matrix production during the menstrual cycle and pregnancy.

Adult↗

Characterization of pig connective tissue growth factor (CTGF) cDNA, mRNA and protein from uterine tissue.

Connective tissue growth factor (CTGF) is a 38kDa mitogen and chemotactic factor for fibroblasts that is transcriptionally activated by serum or transforming growth factor-beta and may play a role in wound healing and various skin diseases. In these studies, pig endometrium was shown to contain a single CTGF transcript of 2.4kb and to produce a 38kDa CTGF-immunoreactive protein. Cloning and sequencing of a 1.5kb pig uterine CTGF cDNA revealed that the predicted pCTGF primary translation product displayed 92% identity to human CTGF and 93% identity to mouse CTGF. The pCTGF cDNA encoded a 26 amino acid signal peptide followed by a 323-residue sequence containing 38 highly conserved cysteine residues. In common with mouse and human CTGF proteins, pCTGF is predicted to resemble a multi-functional mosaic protein that contains four distinct modules.

Amino Acid Sequence↗

Connective tissue growth factor and its correlation to other growth factors in experimental granulation tissue.

Connective tissue growth factor (CTGF) is upregulated in a variety of fibrotic disorders, probably secondary to the activation and production of transforming growth factor-beta (TGF-beta). We have studied the expression of CTGF in a rat wound-healing model using Northern blot, in situ hybridization, and immunohistochemistry. The expression of CTGF mRNA in Northern blot and immunohistochemistry were correlated to the expression of TGF-beta1 and platelet-derived growth factor (PDGF). Northern hybridization showed the maximum expression of CTGF mRNA on day 14, whereas TGF-beta1 expression was maximal on days 7 and 14 and the time-related changes were smaller than for CTGF. PDGF A and PDGF B mRNA expressions were at maximum on day 14 and on day 21, respectively. In situ hybridization showed that fibroblast-like cells expressed CTGF most intensively, expression declining rapidly after day 14. CTGF mRNA and protein were found in blood vessel cells during the first week. In immunohistochemistry, all growth factors were expressed by fibroblast-like cells, macrophage-like cells, and blood vessels but CTGF-positive cells were fewer and were more restricted on days 5 and 7. These results demonstrate that CTGF expression together with TGF-beta and PDGF are up-regulated in wound healing, and CTGF expression in blood vessels suggests that CTGF is involved in angiogenesis.

Animals↗

Hair follicle nevi and accessory tragi: variable quantity of adipose tissue in connective tissue framework.

Controversy exists about the histologic differences between hair follicle nevi and accessory tragi. We examined 10 congenital lesions histologically, possible diagnoses of which were hair follicle nevi or accessory tragi. Two specimens out of the 10 had tiny, mature hair follicles surrounded by thick fibrous root sheaths, a few fat cells, and no cartilage. The subcutaneous fat cells of their bases were segmented by a connective tissue framework. They had histologic features of hair follicle nevi. One specimen had cartilage and abundant fat cells with a connective tissue framework in the nodule, as well as a conglomeration of numerous well-differentiated hair follicles. It possessed both elements of a hair follicle nevus and an accessory tragus. Seven specimens had abundant subcutaneous fat and showed a prominent connective tissue framework. These were typical accessory tragi. The present study suggests that the number of fat cells in the nodule or papule differs between these two conditions. All the lesions studied revealed a connective tissue framework in the subcutaneous fat. Histologic features of both hair follicle nevi and accessory tragi can coexist in a single lesion. Hair follicle nevi may represent incomplete accessory tragi with scant fat cells.

Adipose Tissue↗

Effect of D-penicillamine on collagen, glycosaminoglycans, DNA and RNA of granulation tissue and connective tissue of skin, bone and aorta in rats.

Granulation tissue was produced by subcutaneous implantation of viscose-cellulose sponges on rats. The effect of D-penicillamine 500 mg/kg/day for 10 days on granulation tissue and the connective tissue of skin, bone and aorta was studied ny comparison of treated animals with operated and unoperated controls. In addition, the effect of sponge implantation on intact tissues was studied by comparison between the control groups. The amount of granulation tissue was not affected by D-penicillamine, and the granulomas-DNA content even increased. D-penicillamine increased the amount of salt soluble collagen in all tissues consistent with an inhibition of collagen crosslinking as reflected by increased aldehyde content and alpha/beta chain ratio in soluble skin collagen. Skin appeared to be most sensitive. The content of free hydroxyproline and RNA and the RNA/DNA ratio in skin decreased suggesting a decreased collagen biosynthesis. The hydroxylation of proline and lysine was not affected by the treatment. The water percentage of aorta increased during D-penicillamine treatment, and the 35S-sulphate uptake in the sulphated glycosaminoglycans was stimulated in all tissues, in granulation tissue mainly in the chondroitin-4/6-sulphate fraction. No quantitative glycosaminoglycan changes occurred in granulation tissue. Sponge implantation caused an increase in the amount of salt soluble skin collagen without any change in alpha/beta chain ratio and aldehyde content of purified, soluble collagen. D-penicillamine plus operation reduced the collagen content of aorta. The effects of D-penicillamine on connective tissue compounds may be of importance for its antirheumatic efficacy, but the accompanying effect on normal tissues may imply side effects.

Animals↗

Autoimmune connective tissue disease and connective tissue disease-like illnesses after silicone gel augmentation mammoplasty.

Since first reported in 1982, published anecdotal reports have appeared with increasing frequency of patients in whom autoimmune connective tissue diseases developed after mammary augmentation with silicone gel-filled elastomer envelope-type prostheses. Although scleroderma has been reported most often, other diagnoses have included systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and mixed connective tissue disease. Other patients have ill-defined connective tissue-like illnesses often referred to as "human adjuvant disease." The occurrence of dermatomyositis and polymyositis after silicone breast implants appears to be infrequent. We report two new cases of dermatomyositis after silicone exposure. In addition, a comprehensive review of the literature pertaining to rheumatic disease and silicone gel augmentation mammoplasty is presented to provide some perspective on this highly complicated and controversial subject.

Adult↗

Repair in arterial tissue. 2. Connective tissue changes following an embolectomy catheter lesion. The importance of the endothelial cells to repair and regeneration.

The neointimal hyperplasia following a severe mechanical lesion of the rabbit thoracic aorta was studied by vital staining with Evans blue and transmission electron microscopy. Neointimal tissue covered with endothelium contained organized laminated elastin-rich commective tissue. On the contrary neointimal connective tissue covered with pseudoendothelium was disorganized, with a tendency to fibrosis. Reendothelialization, re-establishment of intimal barrier function and formation of lamellated neointimal connective were parallel events. The importance of a intact subendothelial zone controlling healing processes is discussed. Interaction of endothelium and smooth muscle cells seems to be essential in the regulation of neointimal tissue formation and is probably implicated in a general vascular reactive pattern.

Animals↗

In vitro evaluation of the angiostatic potential of drugs using an endothelialized tissue-engineered connective tissue.

The development of a new pharmacological strategy, the angiostatic therapy, to inhibit solid tumor progression has increased the need of powerful in vitro models to screen the angiostatic potential of new drug candidates. We produced an endothelialized reconstructed connective tissue (ERCT) that promotes the spontaneous formation of a human capillary-like network by coculture of human endothelial cells isolated from umbilical cord or from newborn foreskin, with dermal fibroblasts in a collagen sponge. Three inhibitors of angiogenesis, tamoxifen, ilomastat, and echistatin, were used to assess the efficiency of our ERCT to discriminate, in vitro, an angiostatic potential. The capillary-like structures were characterized by their immunoreactivity to human platelet-endothelial cellular adhesion molecule-1 antibodies and were quantified on histological cross-sections of biopsies taken after 10, 17, 24, and 31 days of culture. A dose-response significant inhibition of the capillary-like formation was detected when increasing concentrations of tamoxifen, ilomastat, or echistatin were added for 1 week to the culture medium of the ERCT. Tamoxifen was found to be angiogenic at 10 microM and to have a cytotoxic effect at 40 microM 1 week after drug removal. Echistatin induced a rapid, slight, and reversible inhibition of capillary-like formation, whereas ilomastat caused a very precocious, strong, and reversible inhibition of angiogenesis. In addition, a 16-h hypoxia promoted the formation of 10 times larger vessels (>300 microm(2)), compared with normoxic condition. These results suggest that our model could be efficiently used to study the long-term angiostatic potential of drugs in vitro in a very physiological environment.

Angiogenesis Inhibitors↗

Connective tissue activation. XXVIII. A connective tissue activating peptide from human urine.

A protein factor in human urine which has the ability to activate connective tissue cells has been identified and partially purified; it appears to be different from epidermal growth factor and IgG. This urinary connective tissue activating factor (CTAP-U) is nondialyzable, labile to protease, stable to thiols, heat, and acid, and has an acidic isoelectric point. Purified preparations of CTAP-U have biologic activities that cause human connective tissue cells to synthesize incremental amounts of 14C-hyaluronic acid, 35S-proteoglycans, and 3H-DNA in vitro. The cell spectrum responsive to this substance includes human synovial cells, human chondrocytes, and skin fibroblasts. CTAP-U does not react with antisera to connective tissue activating peptide-III or to antibodies against IgG or its Fc and Fab fragments. Furthermore, CTAP-U does not cross-react in a radioreceptor assay for insulin, basic somatomedin, or epidermal growth factor-urogastrone. Utilizing standardized isolation conditions, CTAP-U preparations with these properties have been isolated from the urine of 6 normal individuals.

Cartilage↗