Role of carbonic anhydrase II in ectopic calcification.
BACKGROUND
Osteopontin (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.


METHODS
To test this hypothesis, OPN and CAR2 expression and calcification of subcutaneously implanted glutaraldehyde-fixed bovine pericardium (GFBP) were studied in CAR2 mutant mice.


RESULTS
Consistent 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 microg Ca/mg tissue, respectively, at 30 days (P<.001), and 42+/-5 versus 20+/-4 microg 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.


CONCLUSIONS
These results indicate that CAR2 expression is an important regulator of ectopic calcification, potentially by facilitating OPN mediated mineral regression.
Rajachar
Rupak M
RM
Bioengineering Department, University of Washington, Seattle, 98195, USA.
Tung
Elyse
E
Truong
Anh Q
AQ
Look
Amy
A
Giachelli
Cecilia M
CM
D000818:Animals; D002114:Calcinosis / Q000201:enzymology* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000502:physiology*; D002417:Cattle; D005404:Fixatives / Q000737:chemistry; D005976:Glutaral / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D053495:Osteopontin / Q000378:metabolism; D010496:Pericardium / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D016707:Tissue Fixation
D005404:Fixatives; D053495:Osteopontin; D024402:Carbonic Anhydrase II; D002118:Calcium; D005976:Glutaral