| Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. | |
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MedLine Citation:
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PMID: 17160579 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by progressive ectopic bone formation in the spinal ligament. To identify the genes related to ossification affected by mechanical stress during OPLL, analyses using cDNA microarray were carried out using cultured human spinal ligament cells that had been subjected to uniaxial cyclic stretching. Samples were obtained from a total of 14 patients: seven cervical or thoracic OPLL patients and seven control patients. Spinal ligament cells derived from tissues of OPLL (OPLL cells) and control (non-OPLL cells) patients were subjected to uniaxial sinusoidal cyclic stretching (0.5 Hz, 20% stretch) for various time periods (0-9 hours). cDNA microarrays revealed that ranges of distribution of both up- and downregulated genes evoked by cyclic stretching were significantly wider in OPLL cells than in non-OPLL cells. Increases in the mRNA expression of endothelin-1 (ET-1) as well as various marker genes related to ossification were also observed. mRNA expression of ET-1 and alkaline phosphatase was increased by mechanical stress in a time-dependent manner, while addition of ET-1 to static cultures of OPLL cells increased mRNA expression of alkaline phosphatase in a dose-dependent manner. During 9 hours of cyclic stretching, ET-1 release increased to about sixfold the amount observed in nonstretched cells. In non-OPLL cells, neither cyclic stretching nor ET-1 induced any increase in alkaline phosphatase expression. These results suggest that mechanical stress promotes the progression of ossification in OPLL cells through autocrine and/or paracrine mechanisms of ET-1. |
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Authors:
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T Iwasawa; K Iwasaki; T Sawada; A Okada; K Ueyama; S Motomura; S Harata; I Inoue; S Toh; K-I Furukawa |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-12-08 |
Journal Detail:
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Title: Calcified tissue international Volume: 79 ISSN: 0171-967X ISO Abbreviation: Calcif. Tissue Int. Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-12-15 Completed Date: 2007-04-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7905481 Medline TA: Calcif Tissue Int Country: United States |
Other Details:
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Languages: eng Pagination: 422-30 Citation Subset: IM |
Affiliation:
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Department of Orthopedic Surgery, Hirosaki University School of Medicine, Hirosaki, 036-8562, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Alkaline Phosphatase / genetics, metabolism Calcinosis / drug therapy, metabolism Cells, Cultured Cervical Vertebrae Endothelin-1 / antagonists & inhibitors, genetics, metabolism*, pharmacology Ethers / pharmacology Gene Expression / drug effects Gene Expression Profiling Humans Hydrocarbons, Fluorinated / pharmacology Longitudinal Ligaments / drug effects, metabolism*, physiopathology Male Middle Aged Oligonucleotide Array Sequence Analysis Oligopeptides / pharmacology Ossification of Posterior Longitudinal Ligament / metabolism*, physiopathology Piperidines / pharmacology RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Stress, Mechanical Thoracic Vertebrae |
| Chemical | |
Reg. No./Substance:
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0/BQ 788; 0/Endothelin-1; 0/Ethers; 0/Hydrocarbons, Fluorinated; 0/Oligopeptides; 0/Piperidines; 0/RNA, Messenger; 58109-34-5/fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; EC 3.1.3.1/Alkaline Phosphatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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