INTRODUCTION: 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.
INTRODUCTION: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-deficientmice compared to wild types on the C57Bl/6 background. GFBP implanted in CAR2-deficientmice (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.
Authors: Susan A Steitz; Mei Y Speer; Marc D McKee; Lucy Liaw; Manuela Almeida; Hsueh Yang; Cecilia M Giachelli Journal: Am J Pathol Date: 2002-12 Impact factor: 4.307
Authors: A Miyauchi; J Alvarez; E M Greenfield; A Teti; M Grano; S Colucci; A Zambonin-Zallone; F P Ross; S L Teitelbaum; D Cheresh Journal: J Biol Chem Date: 1991-10-25 Impact factor: 5.157
Authors: Mei Y Speer; Marc D McKee; Robert E Guldberg; Lucy Liaw; Hsueh-Ying Yang; Elyse Tung; Gerard Karsenty; Cecilia M Giachelli Journal: J Exp Med Date: 2002-10-21 Impact factor: 14.307
Authors: Song Lu; John V White; Raquel I Judy; Lisa L Merritt; Wan Lu Lin; Xiaoying Zhang; Charalambos Solomides; Ifeyinwa Nwaneshiudu; John Gaughan; Dimitri S Monos; Emilia L Oleszak; Chris D Platsoucas Journal: PLoS One Date: 2019-07-16 Impact factor: 3.240