Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.3.13 (lysyl oxidase)
 1,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intra- and intermolecular covalent cross-linking between collagen fibrils, catalyzed by lysyl oxidase (LOX), determines the mechanical properties of connective tissues; however, mechanisms that regulate the collagen cross-linking according to tissue specificity are not well understood. Here we show that periostin, a secretory protein in the dense connective tissues, promotes the activation of LOX. Previous studies showed that periostin null mice exhibit reduced collagen cross-linking in their femurs, periosteum, infarcted myocardium, and tendons. Presently, we showed that active LOX protein, formed by cleavage of its propeptide by bone morphogenetic protein-1 (BMP-1), was decreased in calvarial osteoblast cells derived from periostin null mice. Overexpression of periostin promoted the proteolytic cleavage of the propeptide, which increased the amount of active LOX protein. The results of co-immunoprecipitation and solid phase binding assays revealed that periostin interacted with BMP-1. Furthermore, this interaction probably resulted in enhanced deposition of BMP-1 on the extracellular matrix, suggesting that this enhanced deposition would lead to cleavage of the propeptide of LOX. Thus, we demonstrated that periostin supported BMP-1-mediated proteolytic activation of LOX on the extracellular matrix, which promoted collagen cross-linking.
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PMID:Interaction between periostin and BMP-1 promotes proteolytic activation of lysyl oxidase. 2018 49

Anodically oxidized titanium surfaces, prepared by spark discharge, have micro-submicron surface topography and nano-scale surface chemistry, such as hydrophilic functional groups or hydroxyl radicals in parallel. The complexity of the surface characteristics makes it difficult to draw a clear conclusion as to which surface characteristic, of anodically oxidized titanium, is critical in each biological event. This study examined the in vitro biological changes, induced by various surface characteristics of anodically oxidized titanium with, or without, release of hydroxyl radicals onto the surface. Anodically oxidized titanium enhanced the expression of genes associated with differentiating osteoblasts and increased the degree of matrix mineralization by these cells in vitro. The phenotypes of cells on the anodically oxidized titanium were the same with, or without, release of hydroxyl radicals. However, the nanomechanical properties of this in vitro mineralized tissue were significantly enhanced on surfaces, with release of hydroxyl radicals by oxidation effects. In addition, the mineralized tissue, produced in the presence of bone morphogenetic protein-2 on bare titanium, had significantly weaker nanomechanical properties, despite there being higher osteogenic gene expression levels. We show that enhanced osteogenic cell differentiation on modified titanium is not a sufficient indicator of enhanced in vitro mineralization. This is based on the inferior mechanical properties of mineralized tissues, without either being cultured on a titanium surface with release of hydroxyl radicals, or being supplemented with lysyl oxidase family members.
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PMID:Enhanced in vitro biological activity generated by surface characteristics of anodically oxidized titanium--the contribution of the oxidation effect. 2599 Sep 32

Matrix metalloproteinase-9 (MMP-9) deletion attenuates collagen accumulation and dilation of the left ventricle (LV) post-myocardial infarction (MI); however the biomechanical mechanisms underlying the improved outcome are poorly understood. The aim of this study was to determine the mechanisms whereby MMP-9 deletion alters collagen network composition and assembly in the LV post-MI to modulate the mechanical properties of myocardial scar tissue. Adult C57BL/6J wild-type (WT; n=88) and MMP-9 null (MMP-9(-/-); n=92) mice of both sexes underwent permanent coronary artery ligation and were compared to day 0 controls (n=42). At day 7 post-MI, WT LVs displayed a 3-fold increase in end-diastolic volume, while MMP-9(-/-) showed only a 2-fold increase (p<0.05). Biaxial mechanical testing revealed that MMP-9(-/-) infarcts were stiffer than WT infarcts, as indicated by a 1.3-fold reduction in predicted in vivo circumferential stretch (p<0.05). Paradoxically, MMP-9(-/-) infarcts had a 1.8-fold reduction in collagen deposition (p<0.05). This apparent contradiction was explained by a 3.1-fold increase in lysyl oxidase (p<0.05) in MMP-9(-/-) infarcts, indicating that MMP-9 deletion increased collagen cross-linking activity. Furthermore, MMP-9 deletion led to a 3.0-fold increase in bone morphogenetic protein-1, the metalloproteinase that cleaves pro-collagen and pro-lysyl oxidase (p<0.05) and reduced fibronectin fragmentation by 49% (p<0.05) to enhance lysyl oxidase activity. We conclude that MMP-9 deletion increases infarct stiffness and prevents LV dilation by reducing collagen degradation and facilitating collagen assembly and cross-linking through preservation of the fibronectin network and activation of lysyl oxidase.
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PMID:Building a better infarct: Modulation of collagen cross-linking to increase infarct stiffness and reduce left ventricular dilation post-myocardial infarction. 2608 Mar 61

This book chapter describes the use of exogenous application of lysyl oxidase (LOX) and bone morphogenetic protein-1 (BMP1) to enhance collagen synthesis and deposition from fibroblasts in culture. The protocol includes the generation of human embryonic kidney (HEK) 293 cell lines overexpressing human LOX and BMP1 constructs in order to obtain supernatants enriched in these factors. Incubation of fibroblast monolayers with these conditioned media strongly increases the capacity of these cells to deposit collagen onto the insoluble extracellular matrix. We also describe the use of these decellularized fibroblast-derived matrices as a substrate for the growth and differentiation of mesenchymal stem cells.
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PMID:Boosting collagen deposition with a lysyl oxidase/bone morphogenetic protein-1 cocktail. 3222 22


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