Document Detail

Endothelin-1 actions on resorption, collagen and noncollagen protein synthesis, and phosphatidylinositol turnover in bone organ cultures.
MedLine Citation:
PMID:  1639010     Owner:  NLM     Status:  MEDLINE    
The effects of endothelin-1 (ET) on several tissues are mediated by prostaglandins. In this study, we investigated the actions of ET on bone and determined whether they are mediated through prostaglandin-dependent pathways. Bone resorption, collagen, and non-collagen protein synthesis and inositol phosphate (IP) production were studied in neonatal mouse calvaria and fetal rat limb bone cultures. The effects of ET in the calvaria model were examined in the presence or absence of the cyclooxygenase inhibitor indomethacin (INDO). Bone resorption was stimulated by ET in the neonatal mouse calvaria, and this effect was inhibited by INDO. 45Ca release in the fetal rat limb bones was not affected by ET. ET stimulated collagen and noncollagen protein synthesis significantly in the calvaria model in the presence but not in the absence of INDO, suggesting that the anabolic effects of ET were masked by endogenous prostaglandin production. ET increased phosphatidylinositol turnover in both bone organ cultures. Although the addition of INDO reduced IP production slightly in the mouse calvaria, it was still significantly stimulated by ET. Our results demonstrate that ET has marked effects on bone tissue in vitro. Effects on resorption appear to be prostaglandin dependent, whereas the anabolic effects were not prostaglandin mediated. The stimulatory effects of ET on protein synthesis could be mediated through the IP signaling pathway. Since ET stimulates both bone resorption and anabolism, this peptide may have a role in the coupling of bone remodeling.
A Tatrai; S Foster; P Lakatos; G Shankar; P H Stern
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Endocrinology     Volume:  131     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1992 Aug 
Date Detail:
Created Date:  1992-09-02     Completed Date:  1992-09-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  603-7     Citation Subset:  AIM; IM    
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
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MeSH Terms
Animals, Newborn
Bone Resorption*
Bone and Bones / embryology,  metabolism*
Calcium / metabolism
Calcium Radioisotopes
Collagen / biosynthesis*
Endothelins / pharmacology*
Indomethacin / pharmacology
Organ Culture Techniques
Phosphatidylinositols / biosynthesis*
Protein Biosynthesis*
Rats, Inbred Strains
Grant Support
Reg. No./Substance:
0/Calcium Radioisotopes; 0/Endothelins; 0/Phosphatidylinositols; 53-86-1/Indomethacin; 7440-70-2/Calcium; 9007-34-5/Collagen

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