Document Detail


Thrombin effects on osteoblastic cells. II. Structure-function relationships.
MedLine Citation:
PMID:  1846537     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Thrombin has been shown to cause in vitro bone resorption and to stimulate osteoblastic cell proliferation, phosphoinositide turnover and cytosolic calcium levels. In the present study, the role of the active site of thrombin in its action on osteoblastic cells was investigated. Either hirudin or (4-amidinophenyl)methanesulfonyl fluoride inhibited, in a dose-dependent manner, the effects of thrombin on human osteoblast-like osteosarcoma cells (G292 and Saos-2 cell lines) and on normal rat calvarial osteoblastic cells. Thrombin-induced stimulation of cell proliferation, cytosolic calcium increases, and stimulation of phosphoinositide metabolism were concomitantly, and to a proportionally similar extent, inhibited. The inhibitors, when present in the absence of thrombin, did not affect the basal levels of cell functions. Both zeta-thrombin and gamma-thrombin, forms resulting from proteolytic cleavage of alpha-thrombin, were capable of stimulating the osteoblastic cells. These data indicate that thrombin's actions on osteoblast-like cells are dependent on the availability of its catalytic site.
Authors:
D N Tatakis; C Dolce; R Dziak; J W Fenton
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  174     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  1991 Jan 
Date Detail:
Created Date:  1991-02-22     Completed Date:  1991-02-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  181-8     Citation Subset:  IM    
Affiliation:
Department of Oral Biology, School of Dental Medicine, State University of New York, Buffalo 14214.
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MeSH Terms
Descriptor/Qualifier:
Animals
Binding Sites
Calcium / metabolism
Cell Division
Hirudins / pharmacology
Humans
Osteocytes / drug effects*
Phosphatidylinositols / metabolism
Rats
Structure-Activity Relationship
Thrombin / pharmacology*
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
DE00158/DE/NIDCR NIH HHS; DE07034/DE/NIDCR NIH HHS; DE08240/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Hirudins; 0/Phosphatidylinositols; 7440-70-2/Calcium; EC 3.4.21.5/Thrombin

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


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