Bile Synthesis In Rat Models Of Inflammatory Bowel Diseases
acid synthesis; acute-phase response; acute-phase response; bile synthesis; cholesterol 7-alpha hydroxylase; cholesterol 7-alpha-hydroxylase gene; colitis; crohns-disease; experimental; General & Internal Medicine; inflammatory bowel disease; intestinal inflammation; messenger-rna; nitric-oxide; Research & Experimental Medicine; sulfonic-acid; ulcerative-colitis
Dikopoulos N; Schmid R M; Bachem M; Buttenschoen K; Adler G; Chiang J Y L; Weidenbach H
European Journal of Clinical Investigation
2007
2007-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1111/j.1365-2362.2007.01779.x" target="_blank" rel="noreferrer noopener">10.1111/j.1365-2362.2007.01779.x</a>
Cysteinyl leukotriene 2 receptor promotes endothelial permeability, tumor angiogenesis, and metastasis.
*angiogenesis; *cysteinyl leukotriene receptors; *endothelial cells; *metastasis; *tumor growth; Male; Animals; Mice; Gene Knockout Techniques; Lung Neoplasms/drug therapy; Neoplasm Transplantation; Neoplasms; Receptors; Inbred C57BL; Neovascularization; Experimental; Capillary Permeability/drug effects; Cyclohexanecarboxylic Acids/pharmacology; Endothelial Cells/*drug effects; Leukotriene Antagonists/pharmacology; Neoplasm Metastasis/drug therapy; Phthalic Acids/pharmacology; Leukotriene/drug effects/*metabolism; Pathologic/*chemically induced/drug therapy
Cysteinyl leukotrienes (cys-LTs) are proinflammatory mediators that enhance vascular permeability through distinct receptors (CysLTRs). We found that CysLT2R regulates angiogenesis in isolated mouse endothelial cells (ECs) and in Matrigel implants in WT mice and enhances EC contraction and permeability via the Rho-dependent myosin light chain 2 and vascular endothelial (VE)-cadherin axis. Since solid tumors utilize aberrant angiogenesis for their growth and metastasis and their vessels exhibit vascular hyperpermeability, we hypothesized that CysLT2R, via its actions on the endothelium, might regulate tumor growth. Both tumor growth and metastases of adoptively transferred syngeneic Lewis lung carcinoma (LLC) cells are significantly reduced in CysLT2R-null mice (Cysltr2 (-/-)) compared with WT and CysLT1R-null mice (Cysltr1 (-/-)). In WT recipients of LLC cells, CysLT2R expression is significantly increased in the tumor vasculature, compared with CysLT1R. Further, the tumor vasculature in Cysltr2 (-/-) recipients exhibited significantly improved integrity, as revealed by increased pericyte coverage and decreased leakage of i.v.-administered Texas Red-conjugated dextran. Administration of a selective CysLT2R antagonist significantly reduced LLC tumor volume, vessel density, dextran leakage, and metastases in WT mice, highlighting CysLT2R as a VEGF-independent regulator of the vasculature promoting risk of metastasis. Thus, both genetic and pharmacological findings establish CysLT2R as a gateway for angiogenesis and EC dysregulation in vitro and ex vivo and in an in vivo model with a mouse tumor. Our data suggest CysLT2R as a possible target for intervention.
Duah Ernest; Teegala Lakshminarayan Reddy; Kondeti Vinay; Adapala Ravi K; Keshamouni Venkateshwar G; Kanaoka Yoshihide; Austen K Frank; Thodeti Charles K; Paruchuri Sailaja
Proceedings of the National Academy of Sciences of the United States of America
2019
2019-01
<a href="http://doi.org/10.1073/pnas.1817325115" target="_blank" rel="noreferrer noopener">10.1073/pnas.1817325115</a>
Tissue engineering models of human digits: effect of periosteum on growth plate cartilage development.
*Models; *Tissue Engineering; Animals; Articular/*growth & development; Biological; Cartilage; Cattle; Experimental; Fingers/diagnostic imaging; Growth Plate/cytology/*growth & development; Humans; Implants; Male; Mice; Nude; Periosteum/*physiology; Radiography
Tissue-engineered middle phalanx constructs of human digits were investigated to determine whether periosteum wrapped partly about model midshafts mediated cartilage growth plate formation. Models were fabricated by suturing ends of polymer midshafts in a human middle phalanx shape with polymer sheets seeded with heterogeneous chondrocyte populations from bovine articular cartilage. Half of each midshaft length was wrapped with bovine periosteum. Constructs were cultured, implanted in nude mice for up to 20 weeks, harvested and treated histologically to assess morphology and cartilage proteoglycans. After 20 weeks of implantation, chondrocyte-seeded sheets adjacent to periosteum-wrapped midshaft halves established cartilage growth plates resembling normal tissue in vivo. Sheets adjacent to midshafts without periosteum had disorganized cells and no plate formation. Proteoglycans were present at both midshaft ends. Periosteum appears to guide chondrocytes toward growth plate cartilage organization and tissue engineering provides means for carefully examining construct development of this tissue.
Landis William J; Jacquet Robin; Lowder Elizabeth; Enjo Mitsuhiro; Wada Yoshitaka; Isogai Noritaka
Cells, tissues, organs
2009
2009
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1159/000151432" target="_blank" rel="noreferrer noopener">10.1159/000151432</a>
Experimental use of fibrin glue to induce site-directed osteogenesis from cultured periosteal cells.
*Fibrin Tissue Adhesive; *Osteogenesis; Animals; Bone and Bones/chemistry/cytology/diagnostic imaging; Cattle; Cells; Cultured; Experimental; Implants; Injections; Mice; Non-programmatic; Nude; Osteopontin; Periosteum/*cytology; Radiography; Sialoglycoproteins/analysis
The purpose of this study was to determine whether a combination of fibrin glue and cultured periosteal cells will result in new bone formation at heterotopic sites in nude mice. Growing cells and developing matrices surrounding periosteal explants from the diaphyses of radii of newborn calves were minced and mixed with fibrin glue in a syringe. The cell/matrix-fibrin glue admixture was then injected into the subcutaneous space on the dorsum of athymic nude mice. After 12 weeks of implantation, gross morphology and histologic investigations showed newly formed bone structures in all cell/matrix-fibrin glue admixtures, but none in fibrin glue injected alone and used as control samples. Osteopontin, a protein important in bone development, was identified by a Western blot assay of the cell/matrix-fibrin glue composite. This study supports the feasibility of initiating site-directed formation of bone structures at heterotopic tissue sites by means of injection of cultured periosteal cells and matrix in a fibrin glue carrier.
Isogai N; Landis W J; Mori R; Gotoh Y; Gerstenfeld L C; Upton J; Vacanti J P
Plastic and reconstructive surgery
2000
2000-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/00006534-200003000-00019" target="_blank" rel="noreferrer noopener">10.1097/00006534-200003000-00019</a>
Development of bone and cartilage in tissue-engineered human middle phalanx models.
*Models; Aggrecans/genetics/metabolism; Animals; Biological; Bone Development/drug effects/*physiology; Calcium Phosphates/pharmacology; Cartilage/cytology/drug effects/*growth & development; Cattle; Chondrocytes/cytology/drug effects/metabolism; Collagen Type II/genetics/metabolism; Durapatite/pharmacology; Electron; Experimental; Finger Phalanges/cytology/diagnostic imaging/drug effects/*physiology; Gene Expression Profiling; Gene Expression Regulation/drug effects; Humans; Implants; Integrin-Binding Sialoprotein; Mice; Microscopy; Paraffin Embedding; Periosteum/cytology/drug effects; Polyesters/pharmacology; Radiography; Scanning; Sialoglycoproteins/genetics/metabolism; Tissue Engineering/*methods; Tissue Scaffolds/chemistry
Human middle phalanges were tissue-engineered with midshaft scaffolds of poly(L-lactide-epsilon-caprolactone) [P(LA-CL)], hydroxyapatite-P(LA-CL), or beta-tricalcium phosphate-P(LA-CL) and end plate scaffolds of bovine chondrocyte-seeded polyglycolic acid. Midshafts were either wrapped with bovine periosteum or left uncovered. Constructs implanted in nude mice for up to 20 weeks were examined for cartilage and bone development as well as gene expression and protein secretion, which are important in extracellular matrix (ECM) formation and mineralization. Harvested 10- and 20-week constructs without periosteum maintained end plate cartilage but no growth plate formation. They also consisted of chondrocytes secreting type II collagen and proteoglycan, and they were composed of midshaft regions devoid of bone. In all periosteum-wrapped constructs at like times, end plate scaffolds held chondrocytes elaborating type II collagen and proteoglycan and cartilage growth plates resembling normal tissue. Chondrocyte gene expression of type II collagen, aggrecan, and bone sialoprotein varied depending on midshaft composition, presence of periosteum, and length of implantation time. Periosteum produced additional cells, ECM, and mineral formation within the different midshaft scaffolds. Periosteum thus induces midshaft development and mediates chondrocyte gene expression and growth plate formation in cartilage regions of phalanges. This work is important for understanding developmental principles of tissue-engineered phalanges and by extension those of normal growth plate cartilage and bone.
Wada Yoshitaka; Enjo Mitsuhiro; Isogai Noritaka; Jacquet Robin; Lowder Elizabeth; Landis William J
Tissue engineering. Part A
2009
2009-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1089/ten.TEA.2009.0078" target="_blank" rel="noreferrer noopener">10.1089/ten.TEA.2009.0078</a>