UMLS:C0001511 - FACTA Search

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Query: UMLS:C0001511 (Adhesion)
5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Adhesion molecules are considered to have an active role in controlling cell differentiation, although the mechanisms involved have yet to be determined. The developing tooth provides an excellent model to use for determining the factors/processes regulating cell differentiation. The studies presented here focused specifically on the timed and spatial expression of a bone-associated adhesion molecule, bone sialoprotein, during tooth root development. Mandibular tissues in the first molar region of CD-1 mice, at sequential stages of development, were analysed by in situ hybridization. The results demonstrate distinct expression of bone sialoprotein in surrounding bone at early stages of tooth development. At stages of active cementogenesis, bone sialoprotein transcripts were specific to cells lining the root surface, with limited expression in the surrounding connective tissue (periodontal ligament) region. The strong expression of bone sialoprotein, a mineral-specific protein having the capacity to act as a nucleator of hydroxyapatite in vitro, by cells lining the root surface at early stages of cementogenesis suggests that this molecule is operative in the cell/matrix events that accompany cementum formation.
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PMID:Expression of bone sialoprotein mRNA by cells lining the mouse tooth root during cementogenesis. 902 20

Adhesion, spreading, and focal contact formation of primary bone-derived cells on quartz surfaces grafted with a 15 amino acid peptide that contained a -RGD-(-Arg-Gly-Asp-) sequence unique to bone sialoprotein was investigated. The peptide surfaces were fabricated by using a heterbifunctional crosslinker, sulfosuccinimidyal 4-(N-maleimidomethyl)cyclohexane-1-carboxylate, to link the peptide to amine functionalized quartz surfaces. Contact angle measurements, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy were used to confirm the chemistry and thickness of the overlayers. A radial flow apparatus was used to characterize cell detachment from peptide-grafted surfaces. After 20 min of cell incubation, the strength of cell adhesion was significantly (p < 0.05) higher on the -RGD- compared to -RGE- (control) surfaces. Furthermore, the mean area of cells contacting the -RGD- was significantly (p < 0.05) higher than -RGE- surfaces. Vinculin staining showed formation of small focal contact patches on the periphery of bone cells incubated for 2 h on the -RGD- surfaces; however, few or no focal contacts were formed by cells seeded on the -RGE-grafted surfaces. The methods of peptide immobilization utilized in this study can be applied to implants, biosensors, and diagnostic devices that require specificity in cell adhesion.
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PMID:The detachment strength and morphology of bone cells contacting materials modified with a peptide sequence found within bone sialoprotein. 933 44

Evidence is mounting that changes in the ability of cancer cells to adhere to extracellular matrices play a decisive role in metastatic spread. The mechanism underlying the preference of breast cancer cells to metastasize to bone is, however, poorly understood. We investigated the expression and involvement of integrin adhesion receptors in the adhesion of breast cancer cells to bone matrix (constituents) in two in vitro attachment assays using RGD peptides and anti-integrin antibodies. Breast cancer cells adhered rapidly to extracellular bone matrix. Adhesion of most cells to vitronectin, fibronectin, thrombospondin, osteopontin, and the fairly bone-specific bone sialoprotein was inhibited by the 200 micrograms/ml GRGDS peptide. These data suggest that integrin adhesion receptors can modulate the attachment of breast cancer cells to bone matrix molecules. In accordance with these findings, we found that alpha 1-alpha 5(beta 1) and alpha v(beta 3) integrins were expressed by mammary carcinoma cells. Highly tumorigenic MDA-MB-231 cells, which form osteolytic metastases in vivo, expressed relatively high levels of alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha v beta 3 integrins, when compared to MCF-7, T47D, and ZR75-1 breast cancer cells. Addition of function-blocking anti-alpha 2 beta 1, -alpha 3 beta 1, -alpha 5 beta 1, and -alpha v beta 3 antibodies significantly inhibited the adhesion of MDA-MB-231 breast cancer cells to bone matrices. In conclusion, our data suggest a possible role for beta 1 and beta 3 integrin subfamily members in the establishment of skeletal metastases in advanced breast cancer patients. Clearly, functional evidence is required to understand the mechanisms involved in the development of skeletal metastases in breast cancer patients.
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PMID:Attachment characteristics and involvement of integrins in adhesion of breast cancer cell lines to extracellular bone matrix components. 942 5

Bisphosphonates (BPs) are potent inhibitors of bone resorption and are therapeutically effective in disease of increased bone turnover, but their mechanism(s) of action remain to be elucidated. Using as experimental model human osteoclast-like cell lines derived from giant cell tumors of bone, extensively characterized for their osteoclast features, we investigated the adhesive properties of osteoclasts on bone slices and on different proteins of the extracellular matrix in the presence of BPs. Adhesion assays using bone slices pretreated with ALN, at the established active concentration, showed that, although the morphology of osteoclasts plated onto pretreated bone slices was not modified, the number of adherent cells was reduced by the treatment of about 50% vs. controls. The effect of ALN on the adhesion of osteoclast-like cells onto specific extracellular matrix proteins, such as bone sialoprotein-derived peptide, containing the RGD sequence, conjugated to BSA (BSP-BSA) and fibronectin (FN), was also tested. In the case of FN the treatment with ALN of protein-coated wells did not modify the percentage of cell adhesion compared with the control, whereas onto BSP-BSA the presence of ALN significantly reduced adhesion of about 40-45%, suggesting that the inhibitory effect of ALN on cell adhesion could probably be due to the interference with receptors specifically recognizing bone matrix proteins as alphaVbeta3 integrins. Furthermore, ALN induced Ca-mediated intracellular signals in osteoclasts, triggering a 2-fold increase in intracellular calcium concentration.
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PMID:Alendronate reduces adhesion of human osteoclast-like cells to bone and bone protein-coated surfaces. 970 27

The biocompatibility of two implantable materials, zirconia and alumina ceramics, was investigated in vitro using human osteoblast cell cultures. The viability of osteoblast cells with the materials was evaluated by the methylthiazole sulfate test that revealed an absence of any cytostatic or cytotoxic effect. Cell proliferation kinetic and total protein synthesis in osteoblasts with zirconia or alumina were similar to that observed in control cells cultured on glass coverslips. Light and scanning electron microscopic examinations showed an intimate contact between osteoblasts and the substrates; well-spread cells were observed on the surfaces of both materials. Adhesion ability and morphological characteristics were preserved in osteoblast cultures with these substrates. Moreover, immunohistochemical staining in osteoblasts with zirconia and alumina showed the capacity of these cells to elaborate the extracellular matrix composed of types I and V collagen, osteocalcin, osteonectin, bone sialoprotein, and cellular fibronectin. Finally, DNA image cytometry and interphase silver-nucleolar organizer regions quantification were applied as complementary biocompatibility tests to detect any changes in DNA synthesis and cell proliferation, respectively. The results showed that neither material altered cell ploidy or cell growth rate in accordance with the absence of any inducing effect on DNA synthesis or proliferation.
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PMID:In vitro reactions of human osteoblasts in culture with zirconia and alumina ceramics. 1049 83

In osteoarthritis (OA), cartilage and bone fragments have been described within the synovial tissue which are surrounded by synovial cells (i.e. detritus synovitis). These cells appear to attach actively to the cartilage and bone fragments. In rheumatoid arthritis (RA), on the other hand, synovial fibroblasts (SF) have also been shown to be localized at sites of invasion into cartilage and bone and to degrade extracellular matrix (ECM) by secreting proteolytic enzymes. One prerequisite for exerting their aggressive properties is the attachment to cartilage and bone ECM. This attachment appears to be mediated by the expression of different adhesion molecules for which corresponding binding sites on ECM components are known. As it has not been addressed to which ECM proteins SF adhere and with which affinity this process takes place, we investigated the adherence of SF from patients with OA and RA to different cartilage and bone matrix proteins. Synovial tissue samples were obtained during synovectomy or arthroplastic surgery and used for isolating and culturing SF. Synovial cells attaching to cartilage/bone fragments were characterized using immunohistochemistry. The adherence of SF to ECM proteins was examined using an adhesion assay with the following proteins coated on 96-well plates: aggrecan (AGG), bone sialoprotein (BSP), cartilage oligomeric matrix protein (COMP), collagen type I, II and VI, proline arginine-rich, end leucine-rich repeat protein (PRELP), osteopontin (OPN) and recombinant chondroadherin (CHAD). Bovine serum albumin was used as negative control. In addition, adhering fibroblasts were photographed using a phase-contrast microscope. As compared with RA-SF, significantly higher numbers of OA-SF adhering to collagen type II, OPN and CHAD could be detected (P < 0.05). In contrast, RA-SF showed increased attachment to collagen type II, OPN and BSP. Adhesion to AGG, COMP and PRELP appeared not to be significantly increased and differed widely among the SF samples, and, apart from one exception (BSP), OA-SF adhered in higher numbers to the matrix proteins than did RA-SF. Using immunohistochemistry, synovial cells attached to cartilage/bone fragments could be shown to predominantly express CD68 (>/=50%). The CD68-negative population was of the fibroblast phenotype (AS02 positive). The study demonstrates that the binding pattern of OA-SF and RA-SF to ECM proteins differs considerably and therefore provides novel insights into the difficult pathophysiology of OA and RA. In general, it appeared that SF adhere primarily to ECM proteins that contain known binding sites for adhesion molecules (e.g. integrins: collagen/integrin alpha(2)beta(1)) and that higher numbers of OA-SF adhered to the cartilage and bone matrix proteins than did RA-SF.
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PMID:Differential adherence of osteoarthritis and rheumatoid arthritis synovial fibroblasts to cartilage and bone matrix proteins and its implication for osteoarthritis pathogenesis. 1554 Oct 45

Polystyrene surfaces grafted with a nonfouling interfacial interpenetrating polymer network (IPN) of poly(acrylamide-co-ethylene glycol/acrylic acid) [p(AAm-co-EG/AAc)] were modified with several peptide ligands adapted from bone sialoprotein (BSP). IPNs were modified with both single ligands and ligand blends to study the correlation between a simple metric, ligand-receptor adhesion strength, and the extent of matrix mineralization for osteoblast like cells (rat calvarial osteoblasts). The ligands studied included RGD cell-binding [CGGNGEPRGDTYRAY (l-RGD), CGGEPRGDTYRA (s2-RGD), CGPRGDTYG (lc-RGD), cyclic(CGPRGDTYG) (c-RGD), and CGGPRGDT (s-RGD)], heparin binding (CGGFHRRIKA), and collagen binding (CGGDGEAG) peptides, with the appropriate controls. Adhesion strength scaled with ligand density (1-20 pmol/cm(2)) and was dependent on ligand type with the following trend: l-RGD > s2-RGD approximately c-RGD >> s-RGD approximately lc-RGD >>> FHRRIKA approximately DGEA. Independent of ligand density, % matrix mineralization varied with ligand type resulting in the following trend: lc-RGD > s2-RGD > l-RGD approximately c-RGD >> s-RGD >>> FHRRIKA. The Tyr (Y) residue immediately following the RGD cell-binding domain proved to be critical for stable cell proliferation and mineralization, since removal of this residue resulted in erratic cell attachment and mineralization behavior. The minimum BSP sequence necessary for strong adhesion and extensive mineralization was CGGEPRGDTYRA; the minimal sequence suitable for extensive mineralization but lacking strong adhesion was CGPRGDTYG. The cyclic peptide (c-RGD) had much greater adhesion strength compared to its linear counterpart (lc-RGD). The calculated characteristic adhesion strength (F(70)) obtained using a centrifuge adhesion assay proved to be a poor metric for predicting % mineralized area; however, in general, surfaces possessing a F(70) > 100g promoted extensive matrix mineralization. Percent mineralization and number of mineralized nodules scaled with number of cells seeded suggesting a critical dependence on the initial number of osteoprogenitors in culture. This study demonstrates matrix mineralization dependence on ligand type, ligand density, and adhesion strength. The high-throughput character of these surfaces allowed efficient investigation of multiple ligands at multiple densities providing an excellent tool for studying ligand-receptor interactions under normal cell culture conditions with serum present.
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PMID:The effect of ligand type and density on osteoblast adhesion, proliferation, and matrix mineralization. 1612 56

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