Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteonectin is an adhesive glycoprotein synthesized constitutively by osteoblasts, endothelial cells, and megakaryocytes. Bone-derived and platelet-derived osteonectins differ in their electrophoretic mobility and carbohydrate content, and each displays different affinities for collagen matrices. Both types of osteonectin bind to plasminogen (Kd(app), of 4.7 +/- 1.0 x 10(-8) M for bone osteonectin and 1.2 +/- 0.1 x 10(-7) M for platelet osteonectin). The osteonectin-plasminogen interaction is inhibited by alpha 2-antiplasmin and epsilon-aminocaproic acid, suggesting that the interaction is mediated through the kringle 1 region of plasminogen. Both osteonectins enhance the rate of plasmin generation by tissue-type plasminogen activator to approximately the same extent as fibrinogen. Equilibrium binding measurements conducted using total internal reflection fluorescence spectroscopy indicate that plasminogen binds to collagen in the presence of bone osteonectin (Kd = 1.30 +/- 0.1 x 10(-7) M). No binding of plasminogen to collagen matrix was detected in the presence of platelet osteonectin or in the absence of bone osteonectin. Bone osteonectin-dependent binding of plasminogen to collagen matrix is reversed by the addition of epsilon-aminocaproic acid. The ability of both types of osteonectin to bind to and influence plasminogen activation and of bone osteonectin to anchor plasminogen on collagen matrices suggests that osteonectin may play a role in directing extracellular matrix proteolysis.
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PMID:Osteonectin in matrix remodeling. A plasminogen-osteonectin-collagen complex. 798 19

In situ crosslinkable biomaterials with degradation profiles that can be tailored to a particular application are indispensable for treating irregularly shaped defects and for fabrication of shape-selective scaffolds. The objective of this work was to synthesize ultra low molecular weight functionalized PLA and PLGA macromers that can be grafted with bioactive peptides and crosslinked in situ to fabricate biodegradable functional scaffolds. In situ crosslinkable lactide-co-glycolide macromer (cMLGA; "c" for crosslinkable, "M" for macromer, and "LGA" for lactide-co-glycolide) was synthesized by anionic polymerization of lactide and glycolide monomers followed by condensation polymerization with fumaryl chloride. The cMLA (100% L-lactide) and cMLGA macromers formed porous crosslinked scaffolds with NVP as the crosslinker. The mass loss of the crosslinked cMLA and cMLGA was linear with incubation time in vitro (zero-order degradation) and the degradation rate depended on the ratio of lactide to glycolide. cMLGA scaffold with 1:1 lactide to glycolide ratio completely degraded after 4 weeks while the cMLA lost less than 40% of its initial mass after 35 weeks. When cMLA scaffold was functionalized with acrylated integrin-binding Ac-GRGD amino acid sequence, bone marrow stromal (BMS) cells attached and spread on the cMLA scaffold and exhibited focal-point cell adhesion. The mRNA expression levels of collagen-1alpha, osteonectin, and osteopontin for BMS cells seeded in the scaffolds with 1 and 5% Ac-GRGD were upregulated compared with those without Ac-GRGD. cMLGA is attractive as in situ crosslinkable macromer for fabrication of functional scaffolds with degradation characteristics that can be tailored to a particular application.
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PMID:Material properties and bone marrow stromal cells response to in situ crosslinkable RGD-functionlized lactide-co-glycolide scaffolds. 1843 54

In this study, rabbit adipose-derived stem cells (rASCs) were isolated, cultured in vitro, and transfected with recombinant adenovirus vector containing human bone morphogenetic protein 2 (Ad-hBMP2). These cells were combined with a nano-hydroxyapatite/recombinant human-like collagen/poly(lactic acid) scaffold (nHA/RHLC/PLA) to fabricate a new biocomposite (hBMP2/rASCs-nHA/RHLC/PLA, group 1) and cultured in osteogenic medium. Non-transfected rASCs mixed with nHA/RHLC/PLA (rASCs-nHA/RHLC/PLA, group 2) and nHA/RHLC/PLA scaffold alone (group 3) served as controls. Scanning electron microscope (SEM) demonstrated integration of rASCs with the nHA/RHLC/PLA scaffold. Quantitative real-time RT-PCR analyses of collagen I, osteonectin, and osteopontin cDNA expression indicated that the osteogenic potency of rASCs was enhanced by transfection with Ad-hBMP2. After in vitro culture for seven days, three groups were implanted into 15-mm length critical-sized segmental radial defects in rabbits. After 12 weeks, radiographic and histological analyses were performed. In group 1, the medullary cavity was recanalised, bone was rebuilt and moulding was finished, the bone contour had begun to remodel and scaffold was degraded completely. In contrast, bone defects were not repaired in groups 2 or 3. Furthermore, the scaffold degradation rate in group 1 was significantly higher than in groups 2 or 3. In summary, after transduction with Ad-hBMP2, the osteogenesis of rASCs was enhanced; a new biocomposite created with these cells induced repair of a critical bone defect in vivo in a relatively short time.
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PMID:Enhanced bone formation in large segmental radial defects by combining adipose-derived stem cells expressing bone morphogenetic protein 2 with nHA/RHLC/PLA scaffold. 2014 Jun 71

To maintain the precise internal milieu of the mammalian central nervous system, well-controlled transfer of molecules from periphery into brain is required. Recently the soluble and cell-surface albumin-binding glycoprotein SPARC (secreted protein acidic and rich in cysteine) has been implicated in albumin transport into developing brain, however the exact mechanism remains unknown. We postulate that SPARC is a docking site for albumin, mediating its uptake and transfer by choroid plexus epithelial cells from blood into cerebrospinal fluid (CSF). We used in vivo physiological measurements of transfer of endogenous (mouse) and exogenous (human) albumins, in situ Proximity Ligation Assay (in situ PLA), and qRT-PCR experiments to examine the cellular mechanism mediating protein transfer across the blood-CSF interface. We report that at all developmental stages mouse albumin and SPARC gave positive signals with in situ PLAs in plasma, CSF and within individual plexus cells suggesting a possible molecular interaction. In contrast, in situ PLA experiments in brain sections from mice injected with human albumin showed positive signals for human albumin in the vascular compartment that were only rarely identifiable within choroid plexus cells and only at older ages. Concentrations of both endogenous mouse albumin and exogenous (intraperitoneally injected) human albumin were estimated in plasma and CSF and expressed as CSF/plasma concentration ratios. Human albumin was not transferred through the mouse blood-CSF barrier to the same extent as endogenous mouse albumin, confirming results from in situ PLA. During postnatal development Sparc gene expression was higher in early postnatal ages than in the adult and changed in response to altered levels of albumin in blood plasma in a differential and developmentally regulated manner. Here we propose a possible cellular route and mechanism by which albumin is transferred from blood into CSF across a sub-population of specialised choroid plexus epithelial cells.
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PMID:Cellular specificity of the blood-CSF barrier for albumin transfer across the choroid plexus epithelium. 2521 95