Direct modulatory effect of hexasodium N,N,N',N'-ethylenediamine-tetramethylene-phosphonate on bone cell function in vitro.
The phosphonate hexasodium N,N,N',N'-ethylenediamine-tetramethylenephosphonate (EDITEMP.Na6) reduced alkaline phosphatase (Alp) activity and cAMP response to parathyroid hormone (PTH) in primary cultures of foetal rat calvaria cells in a dose-dependent manner, while not affecting culture DNA content. EDITEMP.Na6 also inhibited the mineralization of three-dimensional bone nodules formed in vitro, but not the number of nodules formed. Bone cell culture DNA content was also reduced by EDITEMP.Na6 but at concentrations in excess of those needed to modulate osteoblastic cell function. Withdrawal of EDITEMP.Na6 led to slow but complete recovery of Alp activity. At EDITEMP.Na6 concentrations of 25 microM and higher, recovery of Alp activity appeared to be independent of protein and/or DNA synthesis. Cell culture acid phosphatase (Acp) activity was not affected by EDITEMP.Na6. The results indicate that EDITEMP.Na6 has a direct inhibitory effect on (mature) osteoblastic cell function. In the presence of bone tissue this inhibition also occurred, although not at a relatively low dose level.
Moore
N C
NC
School of Biochemistry, University of Birmingham, England.
Chipman
J K
JK
D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D003864:Depression, Chemical; D008297:Male; D009924:Organ Culture Techniques; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012886:Skull / Q000166:cytology
D009943:Organophosphorus Compounds; D010281:Parathyroid Hormone; C018940:(ethylenedinitrilo)-tetramethylenephosphonic acid; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase