pubmed-article:15138266 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:15138266 | lifeskim:mentions | umls-concept:C0024375 | lld:lifeskim |
pubmed-article:15138266 | lifeskim:mentions | umls-concept:C0029418 | lld:lifeskim |
pubmed-article:15138266 | lifeskim:mentions | umls-concept:C0009325 | lld:lifeskim |
pubmed-article:15138266 | lifeskim:mentions | umls-concept:C1456820 | lld:lifeskim |
pubmed-article:15138266 | lifeskim:mentions | umls-concept:C0333562 | lld:lifeskim |
pubmed-article:15138266 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
pubmed-article:15138266 | pubmed:issue | 29 | lld:pubmed |
pubmed-article:15138266 | pubmed:dateCreated | 2004-7-12 | lld:pubmed |
pubmed-article:15138266 | pubmed:abstractText | Tumor necrosis factor-alpha (TNF-alpha) inhibits osteoblast function in vitro by inhibiting collagen deposition. Studies generally support that TNF-alpha does not inhibit collagen biosynthesis by osteoblasts but that collagen deposition is in some way diminished. The study investigated TNF-alpha regulation of biosynthetic enzymes and proteins crucial for posttranslational extracellular collagen maturation in osteoblasts including procollagen C-proteinases, procollagen C-proteinase enhancer, and lysyl oxidase. The working hypothesis is that such regulation could inhibit collagen deposition by osteoblasts. We report that in phenotypically normal MC3T3-E1 osteoblasts, TNF-alpha decreases collagen deposition without decreasing collagen mRNA levels or procollagen protein synthesis. Analyses of the cell layers revealed that TNF-alpha diminished the levels of mature collagen cross-links, pyridinoline and deoxypyridinoline. Further analyses revealed that the mRNA expression for lysyl oxidase, the determining enzyme required for collagen cross-linking, is down-regulated by TNF-alpha in a concentration- and time-dependent manner by up to 50%. The decrease was accompanied by a significant reduction of lysyl oxidase protein levels and enzyme activity. By contrast, Northern and Western blotting studies revealed that procollagen C-proteinases bone morphogenic protein-1 and mammalians Tolloid and procollagen C-proteinase enhancer were expressed in MC3T3-E1 cells and not down-regulated. The data together demonstrate that TNF-alpha does not inhibit collagen synthesis but does inhibit the expression and activity of lysyl oxidase in osteoblasts, thereby contributing to perturbed collagen cross-linking and accumulation. These studies identify a novel mechanism in which proinflammatory cytokine modulation of an extracellular biosynthetic enzyme plays a determining role in the control of collagen accumulation by osteoblasts. | lld:pubmed |
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pubmed-article:15138266 | pubmed:language | eng | lld:pubmed |
pubmed-article:15138266 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15138266 | pubmed:citationSubset | IM | lld:pubmed |
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pubmed-article:15138266 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:15138266 | pubmed:month | Jul | lld:pubmed |
pubmed-article:15138266 | pubmed:issn | 0021-9258 | lld:pubmed |
pubmed-article:15138266 | pubmed:author | pubmed-author:Palamakumbura... | lld:pubmed |
pubmed-article:15138266 | pubmed:author | pubmed-author:TrackmanPhili... | lld:pubmed |
pubmed-article:15138266 | pubmed:author | pubmed-author:KesslerEfratE | lld:pubmed |
pubmed-article:15138266 | pubmed:author | pubmed-author:PischonNicole... | lld:pubmed |
pubmed-article:15138266 | pubmed:author | pubmed-author:DarboisLauren... | lld:pubmed |
pubmed-article:15138266 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:15138266 | pubmed:day | 16 | lld:pubmed |
pubmed-article:15138266 | pubmed:volume | 279 | lld:pubmed |
pubmed-article:15138266 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:15138266 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:15138266 | pubmed:pagination | 30060-5 | lld:pubmed |
pubmed-article:15138266 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
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pubmed-article:15138266 | pubmed:year | 2004 | lld:pubmed |
pubmed-article:15138266 | pubmed:articleTitle | Regulation of collagen deposition and lysyl oxidase by tumor necrosis factor-alpha in osteoblasts. | lld:pubmed |
pubmed-article:15138266 | pubmed:affiliation | Department of Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, Massachussetts 02118, USA. | lld:pubmed |
pubmed-article:15138266 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:15138266 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
pubmed-article:15138266 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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