Abstract
The phosphonate hexasodium N,N,N′,N′-ethylenediamine-tetramethylenephosphonate (EDITEMP · Na 6) 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 · Na 6 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 · Na 6 but at concentrations in excess of those needed to modulate osteoblastic cell function. Withdrawal of EDITEMP · Na 6 led to slow but complete recovery of Alp activity. At EDITEMP · Na 6 concentrations of 25 μM 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 · Na 6. The results indicate that EDITEMP · Na 6 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.
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