Effect of 1-hydroxyethylidene-1,1-bisphosphonate on membrane-mediated calcium phosphate formation in model liposomal suspensions.
The bisphosphonate, 1-hydroxyethylidene-1,1-bisphosphonate (HEBP), was examined for its effect on calcium phosphate precipitation in pH 7.4, 22 degrees C suspensions of 7:2:1 PC:phosphatidylcholine (PC):dicetylphosphate (DCP):cholesterol (Chol) and 7:1:1 PC:phosphatidylserine (PS):Chol liposomes. HEBP (0.5-50 mumol/l) in the suspending medium had little, if any, effect on precipitation that formed inside phosphate-rich (50 mmol/l) aqueous interiors of liposomes as a result of ionophore (X-537A) driven 2.25 mmol/l Ca2+ influxes from the medium. On the other hand, HEBP had a significant negative impact on the subsequent spread of the precipitate into the surrounding medium when the latter was made metastable with 1.5 mmol/l total inorganic phosphate (PO4). The inhibitory effect of HEBP was more strongly felt in the 7PC:1PS:1Chol liposomal suspensions, with only 1 mumol/l HEBP needed to effectively block extraliposomal precipitation compared to 7.5 mumol/l for 7PC:2DCP:1Chol suspensions. Direct encapsulation of HEBP (1-1000 mumol/l) together with PO4 in the aqueous cores of 7PC:2DCP:1Chol liposomes reduced somewhat (approximately 30%) intraliposomal yields and delayed but did not block extraliposomal precipitate development. These results provide a possible physicochemical explanation for the suppression of matrix vesicle initiated mineralization in ectopically-induced osteoid tissue of HEBP treated mice [1]. In particular, the liposome results suggest that membrane phosphatidylserine interactions with mineral may enhance HEBP's effectiveness in vivo.
Skrtic
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National Institute of Dental Research's Research Associate Program, National Institute of Standards and Technology, Gaithersburg, MD 20899.
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D002130:Calcium Phosphates / Q000737:chemistry*; D011232:Chemical Precipitation; D012968:Etidronic Acid / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry*
D002130:Calcium Phosphates; D008081:Liposomes; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous; D012968:Etidronic Acid