Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:031673 (collagen)
 124,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several benign and malignant tumors of bone and cartilage were examined by means of type-specific collagen antibodies in connection with indirect immunofluorescence technique in order to determine wether there is a positive correlation between cell morphology and gene expression as refered to the synthesis of tissue- or cell-specific collagen. In general benign bone and cartilage tumors show the collagen type corresponding to the original maternal tissue. In malignant osteogenic tumors a strong positive correlation was found between morphologic differentiation of osteosarcoma cells and tissue specific collagen synthesarcomas. Unrelated to the grade of differentiation and the type of malignant tumor, collagen type III could be demonstrated in all tumors investigated, occurring rather from vascular stroma than from the tumor cell itself.
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PMID:Immunhistochemical demonstration of different collagen types in the normal epiphyseal plate and in benign and malignant tumors of bone and cartilage. 14 52

Intracellular collagen was detected by electron microscopy in 14 sarcomas including six osteogenic sarcomas, three liposarcomas, three malignant fibrous histiocytomas, one pleomorphic rhabdomyosarcoma, and one childhood rhabdomyosarcoma. It was contained in not only the fibroblastic cells, but also in the osteoblastic, lipoblastic, myofibroblastic, and primitive cells of the various tumors. The banded intracellular collagen fibrils were observed in large phagocytic vesicles and in smaller membrane-bound vesicles which also appeared to fuse with lysosomes. Residual banding could be seen as well in many such phagolysosomes. Banded collagen was also noted in a primary explant in tissue culture. These findings suggest that the configurations of intracellular collagen seen, are parts of a continuum of a secondary pathway of collagen degradation in mesenchymal tissue and that pathway is one factor indicating a close interrelationship between these sarcomas.
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PMID:Intracellular collagen fibrils in human sarcomas. 21 51

Medullary bone was induced in male Japanese quail by administration of estradiol valerate. An increase in the organic weight of the femur was observed by 36 h after estrogen and an increase in ash weight was observed by 96 h. A complex sequence of metabolic changes in the femur occurred after estrogen treatment. A large increase in uptake of 3H-proline associated with enhanced collagen formation began 36 h after estrogen and reached a peak 3.5 times the control rate at 60 h. The onset of mineralization of the newly formed bone matrix, as determined by 45Ca uptake, began about 24 h after onset of collagen synthesis indicating that synthesis of the bone matrix and its mineralization occur sequentially. Large increases in the rates of uptake of 3H-uridine and 3H-thymidine occurred prior to the onset of medullary bone formation and appear to reflect the differentiation of osteogenic precursors to bone-forming cells.
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PMID:Estrogen-induced sequential changes in avian bone metabolism. 59 53

A single para osteal injection of an aqueous extract of immature bovine bone doubles the diameter of the rat radius and ulna, within 7 days. Bone is formed by activation and prolifeation of cells in the cambium layer of the periosteum. The fibrous periosteum remains intact and appears to adapt by stretching. New trabeculae are oriented radailly about the diphyses. The organic matrix, mainly new bone collagen is elaborated primarly during the first 72 hours and mineralized, in the last 4 days of study. The response is interpreted as an example of cell activation, rather than osteogenic induction and demonstrates tha rapid and massive osteogensis can be trigegered by an appropriate exogenous stimulus.
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PMID:Activation of the resting periosteum. 60 91

An electron microscopic study was made to determine (1) the effects of aging on periosteal and endosteal bone surfaces and (2) whether the membrane-like arrangement of osteoblasts at bone surfaces was retained during aging. Short-lived BNL inbred Swiss albino mice 5 to 130 weeks of age were perfused with glutaraldehyde. Femoral samples were taken and fixed in cold glutaraldehyde, decalcified in EDTA, and postfixed in OsO4. Epon sections were cut and stained with uranyl acetate and lead citrate. In young mice, during bone formation a zone of osteoid was observed while the preosseous zone above consisted of young collagen fibers in formation. The osteoblasts formed a tight membrane-like structure at all bone surfaces. Where bone formation did not occur, single and multiple osmiophilic laminae were observed. With increasing age collagen formation became diminished as did the width of the preosseous and osteoid zones. Subsequently, the zones disappeared. Increased surface structural complexity was seen in some areas, while other areas revealed simplification with advancing age. This depended upon the net accretionary or resorptive activity at a given surface. The membrane-like arrangement of osteogenic cells was lost in 104-week-old animals, exposing bone surfaces to physio-chemical changes not under cellular control and biofeedback.
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PMID:Electron microscopic study of bone surface changes during aging. The loss of cellular control and biofeedback. 62 1

An enriched bovine osteogenic protein preparation in combination with bone collagen matrix (osteogenic protein device) was used to effect new bone growth in extraction sites in the presence or absence of titanium dental implants. Incisor and canine teeth were extracted from each of three cynomolgus monkeys, and implants were inserted directly into the sockets without surgical site preparation. The osteogenic protein device induced new bone formation in close apposition to the titanium implants in all trials within 3 weeks. A lesser amount of new bone formation in both sets of control sites was limited to the bony socket walls and not closely apposed to the implant. These data show that the osteogenic protein device is capable of inducing new bone formation in tooth sockets within 3 weeks in the presence or absence of titanium implants. This is the first known demonstration of the therapeutic induction of bone formation in close apposition to metallic implants.
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PMID:Use of bovine osteogenic protein to promote rapid osseointegration of endosseous dental implants. 128 54

We reported previously that a 32-36-kDa osteogenic protein purified from bovine bone matrix is composed of dimers of two members of the transforming growth factor (TGF)-beta superfamily: the bovine equivalent of human osteogenic protein-1 (OP-1) and bone morphogenetic protein-2a, BMP-2a (BMP-2). In the present study, we produced the recombinant human OP-1 (hOP-1) in mammalian cells as a processed mature disulfide-linked homodimer with an apparent molecular weight of 36,000. Examination of hOP-1 in the rat subcutaneous bone induction model demonstrated that hOP-1 was capable of inducing new bone formation with a specific activity comparable with that exhibited by highly purified bovine osteogenic protein preparations. The half-maximal bone-inducing activity of hOP-1 in combination with a rat collagen matrix preparation was 50-100 ng/25 mg of matrix as determined by the calcium content of day 12 implants. Evaluation of hOP-1 effects on cell growth and collagen synthesis in rat osteoblast-enriched bone cell cultures showed that both cell proliferation and collagen synthesis were stimulated in a dose-dependent manner and increased 3-fold in response to 40 ng of hOP-1/ml. Examination of the expression of markers characteristic of the osteoblast phenotype showed that hOP-1 specifically stimulated the induction of alkaline phosphatase (4-fold increase at 40 ng of hOP-1/ml), parathyroid hormone-mediated intracellular cAMP production (4-fold increase at 40 ng of hOP-1/ml), and osteocalcin synthesis (5-fold increase at 25 ng of hOP-1/ml). In long-term (11-17 day) cultures of osteoblasts in the presence of beta-glycerophosphate and L(+)-ascorbate, hOP-1 markedly increased the rate of mineralization as measured by the number of mineral nodules per well (20-fold increase at 20 ng of hOP-1/ml). Direct comparison of TGF-beta 1 and hOP-1 in these bone cell cultures indicated that, although both hOP-1 and TGF-beta 1 promoted cell proliferation and collagen synthesis, only hOP-1 was effective in specifically stimulating markers of the osteoblast phenotype.
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PMID:Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. 132 98

The collagenous extracellular matrix of bone obtained after dissociative extraction with 4 M guanidine-HCl is an optimal substratum for bone induction by osteogenin, a bone morphogenetic protein. As a proteinaceous substratum, this matrix and other collagen-based materials may be immunogenic. Thus, the search and discovery of a non-immunogenic substratum is a necessary prerequisite for the therapeutic application of the principle of bone induction to skeletal repair. Bovine osteogenin, purified greater than 50,000-fold and with an apparent molecular mass of 28-42 kilodaltons, was delivered into nonresorbable porous hydroxyapatite in granular and disc configuration. A total of 328 preparations were bioassayed for osteogenic activity by subcutaneous implantation into 164 Long-Evans rats. Specimens were harvested at day 7, 11 and 21 after implantation and subjected to alkaline phosphatase activity determination and histologic analysis. Osteogenin combined with discs of porous hydroxyapatite induced in vivo differentiation of the osteogenic phenotype in mesenchymal cells invading the three-dimensional porous space of the inorganic substratum. The geometry of the substratum had a profound influence on bone induction, since the expression of the osteogenic phenotype was solely confined in porous hydroxyapatite with disc configuration. Osteogenin did not induce bone differentiation when combined with granules of porous hydroxyapatite with identical pore dimensions. The finding that the biological activity of osteogenin can be restored and delivered by a substratum with defined geometry other than the insoluble collagenous matrix may form the basis of the potential therapeutic application of bone morphogenetic proteins.
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PMID:The critical role of geometry of porous hydroxyapatite delivery system in induction of bone by osteogenin, a bone morphogenetic protein. 132 28

Subcutaneous implantation of demineralized bone matrix initiates a sequence of developmental events, which culminate in endochondral bone formation. During early stages of development of matrix-induced implants, ED1, Ia-positive monocytes-macrophages were observed, suggesting that in the initial phases of the endochondral bone formation cascade, the bone-inductive protein osteogenin and related bone morphogenetic proteins (BMPs) might serve as potent chemoattractants to recruit circulating monocytes. In this investigation, we demonstrate that at concentrations of 10-100 fg/ml (0.3-3 fM), native bovine osteogenin and recombinant human BMP-2B (rhBMP-2B) induce the directed migration of human blood monocytes in vitro. This chemotactic response was associated with expression of BMP binding sites (receptors) on monocytes. About 750 receptors per cell were detected with an apparent dissociation constant of 200 pM. Both osteogenin and rhBMP-2B at higher concentrations (0.1-30 ng/ml) stimulated mRNA expression for an additional regulatory molecule, type beta 1 transforming growth factor (TGF-beta 1) in human monocytes. TGF-beta 1, in turn, is known to induce a cascade of events leading to matrix generation. Monocytes stimulated by TGF-beta are known to secrete a number of chemotactic and mitogenic cytokines that recruit endothelial and mesenchymal cells and promote their synthesis of collagen and associated matrix constituents. TGF-beta 1 in concert with these other cytokines and matrix components regulates chemotaxis, mesenchymal proliferation, differentiation, angiogenesis, and controlled synthesis of extracellular matrix. Our results demonstrate that osteogenin and related BMPs through their profound effects on monocyte recruitment and cytokine synthesis may promote additional successive steps in the endochondral bone formation cascade.
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PMID:Osteogenin and recombinant bone morphogenetic protein 2B are chemotactic for human monocytes and stimulate transforming growth factor beta 1 mRNA expression. 133 47

The osteogenic potential of the two human osteosarcoma cell lines HOS and KHOS; a cell line produced by the transformation of the HOS cells by the Kirsten murine sarcoma virus, was studied in vitro. HOS cells cultured more than 2 weeks formed nodules composed of two morphologically distinct layers, an epithelial-like surface cell layer and a collagen-rich inner cell layer. Alkaline phosphatase (ALPase) activity occurred in the plasma membrane of the surface cell layer, and calcified substances developing along collagen fibers were detected in the collagen-rich inner cell layer. The calcified substances were further examined by analytical electron microscopy and were shown to be hydroxyapatite crystals. In contrast, there was neither ALPase nor the deposition of a calcified substance in the KHOS cells.
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PMID:In vitro differentiation of the human osteosarcoma cell lines, HOS and KHOS. 135 21


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