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

Prolonged glucocorticoid treatment causes osteoporosis in vivo and inhibits bone formation in vitro. We have previously shown that glucocorticoids inhibit calcification and alter osteoblast organization in a mineralizing bone organ culture system. In this study, the effect of glucocorticoids on osteoblast adhesion to bone matrix proteins and integrin expression was examined in primary rat osteoblasts and a transformed rat osteosarcoma-derived cell line ROS 17/2.8. After 24 h of treatment with corticosterone, these cells displayed a concentration-dependent decrease in adhesion to type I collagen and fibronectin. Adhesion was significantly decreased as early as 4 h after glucocorticoid administration. With 100 nM corticosterone treatment for 24 h, inhibition of the adhesion of ROS 17/2.8 cells and primary osteoblasts to fibronectin was 75 +/- 10% and 50 +/- 8%, and inhibition of adhesion to collagen was 31 +/- 10% and 65 +/- 5%, respectively. This effect was specific for osteoblasts, because glucocorticoids did not change the adhesion of fibroblasts. However, glucocorticoids did inhibit the adhesion of all cell types to rat osteonectin. To determine whether the change in osteoblast attachment to collagen and fibronectin was due to an alteration in integrin levels, the plasma membranes of these cells were labeled with [125I]lactoperoxidase, solubilized, and immunoprecipitated with an antibody to beta 1. A 24-h treatment with 100 nM corticosterone caused 80 +/- 2% and 64 +/- 9% decreases in beta 1 levels in primary osteoblasts and ROS 17/2.8 cells, respectively. These results were confirmed with immunofluorescence microscopy, which showed a glucocorticoid-induced decrease in beta 1 staining. Treatment of primary rat osteoblasts and ROS 17/2.8 cells for 72 h with corticosterone also decreased beta 1-integrin messenger RNA levels in a dose-dependent manner. We have demonstrated that the inhibition of integrin expression by glucocorticoids is involved in the decrease in osteoblast adhesion to bone extracellular matrix proteins. These data suggest that integrin modulation may influence osteoblast function and bone formation and, thus, contribute to glucocorticoid-induced osteoporosis.
 ...
PMID:Glucocorticoids inhibit the attachment of osteoblasts to bone extracellular matrix proteins and decrease beta 1-integrin levels. 753 Jun 48

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.
 ...
PMID:Adhesive properties of isolated chick osteocytes in vitro. 872 86

Heparin-binding forms of vitronectin, a multifunctional adhesive glycoprotein, are associated with the extracellular matrix (ECM) at different locations in the body and serve to promote cell adhesion and the regulation of pericellular proteolysis at sites of angiogenesis. In the present study we characterized the interactions of vitronectin with the counter-adhesive protein osteonectin (also termed SPARC or BM40). Osteonectin and vitronectin were both found associated with the ECM of cultured endothelial cells and were localized in vessel wall sections of kidney tissue. In vitro, the heparin-binding multimeric isoform of vitronectin bound to immobilized osteonectin in a saturable manner with half-maximal binding at 30-40 nM. Preincubation of plasma vitronectin with plasminogen activator inhibitor 1 (PAI-1), which provoked multimer formation, induced the binding of vitronectin to osteonectin. Binding was optimal at physiological ionic strength, and binary complexes were stabilized by tissue transglutaminase-mediated cross-linking. In a concentration-dependent fashion, PAI-1, CaCl2, heparin and heparan sulphate, but not other glycosaminoglycans, interfered with the binding of vitronectin to osteonectin. Using vitronectin-derived synthetic peptides as well as mutant forms of recombinant osteonectin, we found that the heparin-binding region of vitronectin interacted with the C-terminal region of osteonectin that contains a high-affinity Ca2+-binding site with counter-adhesive properties. Adhesion of cultured endothelial cells was partly abrogated by osteonectin and was correspondingly reversed by vitronectin in a concentration-dependent manner. These results indicate that specific interactions between vitronectin and osteonectin modulate cell adhesion and might thereby regulate endothelial cell function during angiogenesis.
 ...
PMID:Differential modulation of cell adhesion by interaction between adhesive and counter-adhesive proteins: characterization of the binding of vitronectin to osteonectin (BM40, SPARC). 916 72

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.
 ...
PMID:In vitro reactions of human osteoblasts in culture with zirconia and alumina ceramics. 1049 83

The nature of the extracellular matrix (ECM) is crucial in regulating cell functions via cell-matrix interactions, cytoskeletal organization, and integrin-mediated signaling. In bone, the ECM is composed of proteins such as collagen (CO), fibronectin (FN), laminin (LM), vitronectin (VN), osteopontin (OP) and osteonectin (ON). For bone tissue engineering, the ECM should also be considered in terms of its function in mediating cell adhesion to biomaterials. This study examined ECM production, cytoskeletal organization, and adhesion of primary human osteoblastic cells on biodegradable matrices applicable for tissue engineering, namely polylactic-co-glycolic acid 50:50 (PLAGA) and polylactic acid (PLA). We hypothesized that the osteocompatible, biodegradable polymer surfaces promote the production of bone-specific ECM proteins in a manner dependent on polymer composition. We first examined whether the PLAGA and PLA matrices could support human osteoblastic cell growth by measuring cell adhesion at 3, 6 and 12h post-plating. Adhesion on PLAGA was consistently higher than on PLA throughout the duration of the experiment, and comparable to tissue culture polystyrene (TCPS). ECM components, including CO, FN, LM, ON, OP and VN, produced on the surface of the polymers were quantified by ELISA and localized by immunofluorescence staining. All of these proteins were present at significantly higher levels on PLAGA compared to PLA or TCPS surfaces. On PLAGA, OP and ON were the most abundant ECM components, followed by CO, FN, VN and LN. Immunofluorescence revealed an extracellular distribution for CO and FN, whereas OP and ON were found both intracellularly as well as extracellularly on the polymer. In addition, the actin cytoskeletal network was more extensive in osteoblasts cultured on PLAGA than on PLA or TCPS. In summary, we found that osteoblasts plated on PLAGA adhered better to the substrate, produced higher levels of ECM molecules, and showed greater cytoskeletal organization than on PLA and TCPS. We propose that this difference in ECM composition is functionally related to the enhanced cell adhesion observed on PLAGA. There is initial evidence that specific composition of the PLAGA polymer favors the ECM. Future studies will seek to optimize ECM production on these matrices for bone tissue engineering applications.
 ...
PMID:Extracellular matrix production by human osteoblasts cultured on biodegradable polymers applicable for tissue engineering. 1252 62

Osteonectin is recognised as a marker of metastasis progression in melanoma and has been implicated in the transition from radial to vertical growth phase. A Tetracycline-inducible system was used to regulate Osteonectin protein levels in melanoma cell lines to examine the morphological, biochemical and invasive changes that accompany its altered expression. Assay of protein and phosphorylation changes showed a downregulation of E-cadherin, upregulation of Osteopontin and a corresponding increase in phosphorylation of Focal Adhesion Kinase on Tyr(397) and Tyr(576) concomitant with Osteonectin induction. Melanoma cells overexpressing Osteonectin displayed increased invasive potential, whereas ablation of Osteonectin gene transcription using siRNA suppressed the invasive potential of these cells and resulted in the upregulation of E-cadherin. The recently described interaction of Osteonectin with Integrin Linked Kinase leading to modulation of its activity suggests a mechanism relevant to the loss of E-cadherin and cell adhesion that occurs during melanoma progression. These results indicate a central role for Osteonectin in the regulation of gene expression changes driving the progression of melanoma toward metastasis.
 ...
PMID:Osteonectin downregulates E-cadherin, induces osteopontin and focal adhesion kinase activity stimulating an invasive melanoma phenotype. 1772 18

The aim of this study was to investigate the effect of demineralized dentin matrix (DDM) on dental pulp stem cells (DPSCs) and the potential of complexes with DPSCs and DDM for mineralized tissue formation. Stem cells derived from the dental pulp of healthy pigs aged 18 months were isolated and cultured. DPSCs were incubated with alpha-minimum essential medium treated with DDM extract at 1 mg/ml (DDM1) or 10 mg/ml (DDM10). The concentrations of 3 growth factors in DDM extract was measured by enzyme-linked immunosorbent assay. Adhesion of DPSCs on DDM and hydroxyapatite-tricalcium phosphate (HA-TCP) surfaces was observed using scanning electron microscopy. Cell proliferation was evaluated with cell counting kit-8 and migration by Transwell migration assays. Odontoblastic differentiation was assessed by alkaline phosphatase (ALP) and alizarin red staining, ALP activity and real-time polymerase chain reaction analysis of markers of ALP, runt-related transcription factor 2, type I collagen, dentin matrix acidic phosphoprotein-1, osteonectin and dentin sialophosphoprotein (DSPP). Finally, DPSCs were combined with DDM and placed subcutaneously in nude mice for 12 weeks; DPSCs combined with HA-TCP and DDM alone served as controls. DDM could promote DPSC adhesion, migration and odontoblastic differentiation. Mineralized tissue formation was observed with the DPSC and DDM combination and the DPSC and HA-TCP combination. The mineralized tissue of the DPSC + DDM combination stained positive for DSPP, similar to the dentin tissue. These results indicate that DDM induces DPSC odontoblastic differentiation, suggesting applications for dentin regeneration.
...
PMID:Demineralized Dentin Matrix Induces Odontoblastic Differentiation of Dental Pulp Stem Cells. 2656 5