Document Detail

Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress.
MedLine Citation:
PMID:  17160579     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-12-08
Journal Detail:
Title:  Calcified tissue international     Volume:  79     ISSN:  0171-967X     ISO Abbreviation:  Calcif. Tissue Int.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-15     Completed Date:  2007-04-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905481     Medline TA:  Calcif Tissue Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  422-30     Citation Subset:  IM    
Department of Orthopedic Surgery, Hirosaki University School of Medicine, Hirosaki, 036-8562, Japan.
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MeSH Terms
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
Hydrocarbons, Fluorinated / pharmacology
Longitudinal Ligaments / drug effects,  metabolism*,  physiopathology
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
Reg. No./Substance:
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 Phosphatase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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