Role of carbonic anhydrase II in ectopic calcification

Introduction ontin (OPN) is a potent inhibitor of ectopic calcification. Previous studies suggested that, in addition to blocking apatite crystal growth, OPN promoted regression of ectopic calcification by inducing the expression of acid-generating carbonic anhydrase II (CAR2) in monocyte-derived cells. s t this hypothesis, OPN and CAR2 expression and calcification of subcutaneously implanted glutaraldehyde-fixed bovine pericardium (GFBP) were studied in CAR2 mutant mice. s tent with previous studies in Black Swiss mice, GFBP calcified to a greater extent in OPN-deficient mice compared to wild types on the C57Bl/6 background. GFBP implanted in CAR2-deficient mice (CAR2−/−) were significantly more calcified than those implanted into wild-type mice (CAR2+/+) [37±5 vs. 20±6.5 μg Ca/mg tissue, respectively, at 30 days (P<.001), and 42±5 versus 20±4 μg Ca/mg tissue at 60 days, respectively (P<.001)]. On the other hand, OPN levels within and surrounding the implants were similar in CAR2+/+ and CAR2−/− mice, suggesting that OPN expression in the absence of CAR2 was not sufficient to mitigate ectopic calcification. sions results indicate that CAR2 expression is an important regulator of ectopic calcification, potentially by facilitating OPN mediated mineral regression.