Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recognition that synthetic devices can provide functional replacements for failed teeth, or for previously edentulous areas, has resulted in increased emphasis being placed on understanding of the interactions between synthetic materials and host tissues in order for the success of these devices to be optimized. A key to achievement of an optimal biological interface between the implant and the surrounding tissue is through an understanding of host response to materials. This article reviews the biological requirements for implant-tissue integration, with specific focus on the role of adhesion molecules and cytokines (growth factors) in this process. Adhesion molecule/cytokine interactions are discussed, and in particular the possible role for osteopontin, an adhesion molecule as well as a cytokine, is considered in wound healing. Finally, the causes of peri-implantitis are discussed, and methods of decontamination are presented. The decontamination methods focus on enhancement of cell adhesion and integration to the altered implant surface.
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PMID:Biological requirements for material integration. 128 60

Osteopontin is an arginine-glycine-aspartate containing acidic glycoprotein postulated to mediate adhesion, migration, and biomineralization in diverse tissues. The mechanisms explaining this multifunctionality are not well understood, although it is known that one osteopontin receptor is the alpha v beta 3 integrin. In this work, we studied human smooth muscle cells varying in alpha v beta 3 levels to identify additional osteopontin receptors. We report that, in addition to alpha v beta 3, both alpha v beta 5 and alpha v beta 1 are osteopontin receptors. Moreover, the presence or absence of alpha v beta 3 on the cell surface altered the adhesive and migratory responses of smooth muscle cells to osteopontin. Adhesion of alpha v beta 3-deficient cell populations to osteopontin was only half that of cells containing alpha v beta 3, and migration toward an osteopontin gradient in the Boyden chamber was dependent on cell surface alpha v beta 3. Although alpha v beta 3-deficient smooth muscle cells were unable to migrate to osteopontin, they did migrate significantly in response to vitronectin and fibronectin. These findings represent the first description of alpha v beta 5 and alpha v beta 1 as osteopontin receptors and suggest that, while adhesion to osteopontin is supported by integrins containing beta 1, beta 3, and beta 5, migration in response to osteopontin appears to depend on alpha v beta 3. Thus, interaction with distinct receptors is one mechanism by which osteopontin may initiate multiple functions.
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PMID:The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro. 753 90

Mammalian osteoclasts express three integrin receptors--alpha v beta 3 (vitronectin receptor), alpha 2 beta 1 and alpha v beta 1. The vitronectin receptor recognizes bone matrix proteins, including bone sialoproteins, in an RGD-dependent manner, whereas adhesion to collagen involves beta 1 integrins. Interference with integrin function, by anti-receptor antibodies or RGD-peptides, blocks bone resorption. Data on the mechanism of osteoclast adhesion to sialoproteins and the differential synthesis of osteopontin and bone sialoprotein by osteoclasts is presented. Thus, osteoclasts adhere to both osteopontin and bone sialoprotein with a characteristic irregular morphology with numerous, peripherally placed, actin-rich podosomes. Adhesion is predominantly RGD and beta 3 dependent, though alpha v beta 1 may also be involved in adhesion to bone sialoprotein. KQAGD and AGDV, but not H12, fibrinogen peptides induce osteoclast 'rounding' on osteopontin suggesting there is an alternative anti-adhesive signal to 'RGD.' However, adhesion is not completely inhibited and is not specific for osteopontin as equivalent effects are seen with adhesion to serum. The role of sialoproteins in osteoclast adhesion in situ in the skeleton is complicated by the finding of endogenous synthesis of osteopontin, but not bone sialoprotein, by osteoclasts. The disposition of osteoclast integrins during resorption and the role of integrins and sialoprotein-derived peptides in osteoclast adhesion and function is also reviewed.
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PMID:Interaction of osteopontin with osteoclast integrins. 754 Mar 73

Adhesion molecules and their cell membrane receptors are known to play important regulatory roles in cell differentiation. Consequently, the following experiments were conducted to determine the role of two adhesion molecules, bone sialoprotein (BSP) and osteopontin (OPN) in tooth root formation. Developing murine molar tooth germs at sequential stages of development (developmental days 21-42) were analyzed using immunohistochemical and in situ hybridization techniques. While BSP was localized to alveolar bone and odontoblasts early in development, BSP was distinctly localized to the cemental root surface at latter periods coincident with the initiation of root formation and cementogenesis. Conversely, OPN was distributed in a nonspecific fashion throughout the PDL and the eruption pathway of the forming tooth. In situ hybridization confirmed that cells lining the root surface express BSP. The fact that BSP is specifically localized to the cemental surface suggests that this protein is involved in cementoblast differentiation and/or early mineralization of the cementum matrix. Localization of OPN to non-mineralized tissues further suggests that OPN functions as an inhibitor of mineralization during periodontal ligament formation. These findings collectively suggest that BSP and OPN are intimately involved in the sequence of cellular and molecular events accompanying cementogenesis.
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PMID:Role of two mineral-associated adhesion molecules, osteopontin and bone sialoprotein, during cementogenesis. 755 41

Recombinant wild-type rabbit osteopontin (rOP) and the protein with an aspartate-to-glutamate transposition induced by a point mutation in the rabbit OP cDNA within the Gly-Arg-Gly-Asp-Ser (GRGDS) sequence were expressed in Escherichia coli and purified to homogeneity. P388D1 cells bound rOP in a saturable manner. rOP induced adhesion and haptotaxis of P388D1 cells, whereas mutated rabbit OP (rOPmut) did not. Anti-rOP IgG F(ab')2 and synthetic GRGDS peptide inhibited rOP-mediated adhesion and haptotaxis of P388D1 cells. Fibronectin (FN)-mediated adhesion of P388D1 cells was markedly inhibited in the presence of fluid-phase rOP. Adhesion of P388D1 cells to rOP was significantly inhibited by anti-[alpha-subunits of VLA4 (alpha 4) and VLA5 (alpha 5)] monoclonal antibodies (mAbs), but not by anti-[alpha-subunit of vitronectin (VN) receptor (alpha V) or Mac-1 (alpha M)] mAb. Adhesion of P388D1 cells to FN and VN was significantly inhibited by anti-alpha V mAb but not anti-alpha 4, -alpha 5 or -alpha M mAb. Haptotaxis of P388D1 cells to rOP was significantly inhibited by anti-alpha V mAb, but not by anti-alpha 4, -alpha 5 and alpha M mAbs, whereas that to FN showed no inhibition with all three mAbs. Haptotaxis of P388D1 cells to VN was significantly inhibited by anti-alpha 5 and -alpha V mAbs but not by anti-alpha 4 and -alpha M mAbs. Similar features of inhibition of adhesion and haptotaxis of P388D1 cells to human OP were observed by mAbs. rOP had no chemotactic effect on P388D1 cells. Significant polymorphonuclear leucocyte migration was observed 3-12 h after intradermal injection of rOP into rabbits.
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PMID:Expression of wild-type and mutated rabbit osteopontin in Escherichia coli, and their effects on adhesion and migration of P388D1 cells. 771 85

Osteopontin (OPN) is a secreted phosphoprotein expressed by many tumor cells, as well as a limited set of normal cells. Native OPN has been shown to support cell adhesion in an RGD-peptide-inhibitable fashion. Here we expressed human OPN in E. coli as a recombinant fusion protein with glutathione-S-transferase (GST). We report that the GST-OPN fusion protein has functional activity. PAP2 (ras-transformed, metastatic murine NIH 3T3) and MDA-MB-435 human mammary carcinoma cells bound to GST-OPN in an in vitro cell adhesion assay nearly as well as to native bovine OPN. Adhesion to the recombinant fusion protein was blocked by addition of GRGDS peptide, suggesting that the cells adhere to the recombinant and native OPN proteins by similar, integrin-mediated mechanisms. Adhesion to both sources of OPN also was inhibited by thrombin treatment of the protein. Thrombin cleaves GST from OPN in the fusion protein, and also cleaves internally in OPN, adjacent to the RGD sequence of the protein. Our results suggest that (a) thrombin cleavage of native OPN may be a natural regulator of OPN function, and (b) the majority of OPN cell binding activity is mediated by the RGD sequence in the protein backbone, with little or no requirement for post-translational modifications that occur in native OPN for adhesive function as measured here.
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PMID:Recombinant GST-human osteopontin fusion protein is functional in RGD-dependent cell adhesion. 817 99

Osteoclast interaction with extracellular matrix drives the sequential events that end with bone resorption. However, the role of matrix proteins is not yet fully understood. We studied this problem on human osteoclast-like cells derived from giant cell tumors of bone (GCT cells). On GCT cells we considered cytoskeletal organization, adhesion properties, and integrin expression upon plating in serum-free medium onto fibronectin (FN), collagen (COL), thrombospondin (TSP), bone sialoprotein (BSPII), and osteopontin (OPN). GCT cells promptly adhered and spread on FN, BSPII, and OPN, while only 50% adhered on COL and none on TSP. The integrin beta 1 chain was always associated to focal adhesions, while the alpha v beta 3 heterodimer was detected in focal contacts only upon plating on BSPII, OPN, and FN. The focal clustering of beta 1 was impaired by monensin treatment, indicating that endogenous FN secretion was required to drive beta 1 into focal contacts. Conversely, alpha v beta 3 clustering was also not affected by monensin when cells were plated onto plasma FN. Immunoprecipitation of metabolically labeled GCT cell lysates showed that three different heterodimers (alpha v beta 3, alpha 3 beta 1, and alpha 5 beta 1) were assembled. Adhesion to FN was completely inhibited by beta 1 antibodies at dilutions up to 1:400, while beta 3 antibodies, at similar dilutions, impaired spreading but not adhesion. We conclude that alpha v beta 3 is the main integrin used by GCT cells in bone recognition. We also suggest that selected substrata may induce the release and the organization of endogenous FN that eventually drives the recruitment of a beta 1 integrin receptor into focal contacts.
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PMID:Adhesion properties and integrin expression of cultured human osteoclast-like cells. 818 15

Osteopontin is an Arg-Gly-Asp-containing acidic phosphoprotein recently shown to be upregulated in vascular smooth muscle during rat arterial neointima formation and in human atherosclerotic plaques. Functional studies showed that osteopontin promoted adhesion of both cultured aortic endothelial cells and aortic smooth muscle cells. Adhesion of vascular cells to osteopontin was dose dependent and half maximal when solutions containing 7 and 30 nmol/L osteopontin were used to coat wells for endothelial and smooth muscle cells, respectively. Smooth muscle cells adherent to osteopontin were spread after 60 minutes, whereas endothelial cells remained round, although flattened, at this time point but were spread at 90 minutes. Cell spreading on osteopontin was accompanied by the formation of focal adhesion plaques. A newly developed anti-osteopontin antibody completely inhibited adhesion of both cell types to osteopontin but not to fibronectin or vitronectin. In addition, the peptide GRGDSP blocked adhesion to osteopontin, suggesting that integrins mediate Arg-Gly-Asp-dependent adhesion. Indeed, an antibody against the alpha v beta 3 integrin neutralized adhesion of both endothelium and smooth muscle cells to osteopontin by approximately 50%, demonstrating that alpha v beta 3 is one osteopontin receptor on vascular cells. Osteopontin also promoted the migration of smooth muscle cells in a Boyden-type chamber, with half-maximal effects observed at 77 nmol/L osteopontin. Checkerboard analysis demonstrated that this stimulus was chemotactic in nature. Our findings suggest that osteopontin may be functionally important as an adhesive and chemotactic molecule for vascular cells, particularly when levels of osteopontin are dramatically increased, as is the case after arterial angioplasty and in atherosclerotic plaques.
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PMID:Osteopontin promotes vascular cell adhesion and spreading and is chemotactic for smooth muscle cells in vitro. 829 61

Osteopontin (OPN) is a secreted protein postulated to facilitate vascular smooth muscle cell (VSMC) adhesion and migration. Rat aortic VSMC lines were isolated after infection with recombinant retroviruses harboring OPN sense and antisense constructs. All lines grew normally in monolayer culture. On three-dimensional collagen gels, normal VSMCs and lines containing sense constructs (n=15) or empty vector (n=10) attached to gel and invaded the matrix. Four of five antisense clones did not adhere or invade. Antisense clones had lower OPN levels after stimulation with angiotensin II than sense clones or clones containing the empty vector (antisense, 257+/-102 ng/ml; sense, 473+/-104; vector, 434+/-66). Non-adhering antisense clones had lower mean OPN levels after angiotensin II stimulation (161+/-47 ng/ml) than sense or antisense lines with normal adhesion (486+/-63 ng/ml). The ability to adhere correlated with OPN levels >250 ng/ml. Adhesion and invasion were fully restored with addition of 100 to 200 ng/ml of exogenous OPN and were inhibited in normal VSMCs by incubation with 1 microgram/ml anti-OPN antibody. The autocrine secretion of OPN appears to play an important role in VSMC adhesion, spreading, and invasion.
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PMID:Autocrine secretion of osteopontin by vascular smooth muscle cells regulates their adhesion to collagen gels. 868 50

Different functions have been proposed for osteocytes over time, but it is now generally accepted that their most important task lies in the sensing of strain caused by mechanical loading on bone. The fact that mechanical strain can be sensed as deformation of the extracellular matrix or as fluid shear stress along the cell, in the space between cell membrane and extracellular matrix, requires that osteocytes have close (specialized) contact with the bone matrix. We studied to which extracellular matrix proteins isolated chicken osteocytes adhere and whether this adhesion is mediated by specific cell adhesion receptors called integrins. The adhesive properties of the osteocytes were compared with that of osteoblasts. Osteocytes (and osteoblasts) adhere to the same substrates (i.e., collagen types I and II, collagen fibers, osteopontin, osteonectin, fibronectin, fibrinogen, thrombospondin, and laminin). Cell spreading varied between substrates, from all cells rounded on thrombospondin to all cells fully spread out on osteopontin, osteonectin, vitronectin, fibronectin, fibrinogen, and laminin. The percentage of osteocytes adhered was equivalent to that of osteoblasts adhered on all substrates except osteopontin and vitronectin, where osteocytes adhered less. The adhesion of osteocytes and osteoblasts to osteopontin, osteonectin, vitronectin, and fibrinogen was strongly inhibited, and to fibronectin and laminin moderately, by an RGD peptide. No RGD inhibition was found on collagen. An antibody against chicken integrin alpha v beta 3, the monoclonal antibody (MAb) 23C6, did not interfere with the adhesion of osteocytes and osteoblasts to matrix proteins, whereas an MAb against chicken integrin subunit beta 1 (CSAT) strongly inhibited adhesion to all substrates. Labeling with osteocyte-specific MAbs (OB7.3, OB37.4, and OB37.11) also did not hinder the adhesion of osteocytes to collagen type I, vitronectin, and osteopontin. Adhesion sites on osteocytes were small compared with the large adhesion plaques of osteoblasts, as demonstrated by interference reflection microscopy and immunocytochemically by staining for vinculin. Osteocyte adhesion is analogous to osteoblast adhesion with regard to the range of extracellular matrix proteins to which they adhere. The adhesion is mediated by the integrin subunit beta 1, but other integrins or nonintegrin adhesion receptors are also involved. Osteocytes make contact with the extracellular matrix via small attachment points which colocalize with vinculin. This connection between the bone matrix and the cytoskeleton may be important for osteocytic sensing of mechanical strain, as it supplies a transduction route of extracellular (mechanical) signals into intracellular messages.
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PMID:Adhesive properties of isolated chick osteocytes in vitro. 872 86


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