Document Detail

Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration.
MedLine Citation:
PMID:  20222016     Owner:  NLM     Status:  MEDLINE    
Parathyroid hormone (PTH) strongly stimulates hyaluronan (HA) synthesis and secretion of both normal and carcinogenic cells of the osteoblastic lineage and improves skeletal microarchitecture. HA, a glycosaminoglycan component of the extracellular matrix (ECM), is capable of transmitting ECM-derived signals to regulate cellular function. In this study, we investigated whether the changes of HA metabolism induced by PTH (1-34) and PTH (7-84) peptides in moderately MG-63 and well-differentiated Saos 2 osteosarcoma cell lines, are correlated to their migration capabilities. Our results demonstrate that intermittent PTH (1-34) treatment significantly (P < or = 0.01) supported the migration of MG-63 cells, increased their HA-synthase-2 (HAS2) expression (P < or = 0.001), and enhanced their high-molecular size HA deposition in the pericellular matrix. Both increased endogenous HA production (P < or = 0.01) and treatment with exogenous high-molecular weight HA (P < or = 0.05) correlated to a significant increase of MG-63 cell migration capacity. Transfection with siHAS2 showed that PTH (1-34), mainly through HAS2, enhanced HA and regulated MG-63 cell motility. Interestingly, continuous PTH (1-34) treatment stimulated both Saos 2 cell HAS2 (P < or = 0.001) and HAS1 (P < or = 0.001) isoform expression inhibited their HYAL2 expression (P < or = 0.001) and modestly (P < or = 0.05) enhanced their migration. Therefore, the PTH (1-34) administration mode appears to distinctly modulate the migratory responses of the MG-63 moderately and Saos 2 well-differentiated osteosarcoma cell lines. Conclusively, the obtained data suggest that there is a regulatory effect of PTH (1-34), in an administration mode-dependent manner, on HA metabolism that is essential for osteosarcoma cell migration.
Aikaterini Berdiaki; Georgios A Datsis; Dragana Nikitovic; Aristidis Tsatsakis; Pavlos Katonis; Nikos K Karamanos; George N Tzanakakis
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  IUBMB life     Volume:  62     ISSN:  1521-6551     ISO Abbreviation:  IUBMB Life     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-21     Completed Date:  2010-07-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888706     Medline TA:  IUBMB Life     Country:  England    
Other Details:
Languages:  eng     Pagination:  377-86     Citation Subset:  IM    
Department of Histology, Division of Morphology, School of Medicine, University of Crete, Heraklion, Greece.
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MeSH Terms
Antigens, CD44 / biosynthesis
Cell Line, Tumor
Cell Movement / drug effects*
Glucuronosyltransferase / antagonists & inhibitors
Hyaluronic Acid / metabolism*
Osteosarcoma / metabolism*
Parathyroid Hormone / pharmacology*
RNA, Small Interfering / pharmacology
Reg. No./Substance:
0/Antigens, CD44; 0/CD44 protein, human; 0/Parathyroid Hormone; 0/RNA, Small Interfering; 9004-61-9/Hyaluronic Acid; EC 2.4.1.-/HAS2 protein, human; EC

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