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Osteoprotegerin (OPG) inhibits vascular calcification in vivo
Author(s) -
Morony Sean,
Zhang Zina,
Cattley Russ,
Dwyer Denise,
Stolina Marina,
Kostenuik Paul,
Tintut Yin,
Demer Linda L.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a653-a
Subject(s) - osteoprotegerin , calcification , in vivo , medicine , chemistry , biology , receptor , microbiology and biotechnology , activator (genetics)
Vascular calcification shares many features with bone mineralization. Recent evidence suggests that it may be governed by two factors now known to critically regulate bone metabolism: RANKL, a TNF‐alpha superfamily member and its soluble decoy receptor, OPG. Both OPG and RANKL are expressed in human arteries, RANKL is increased in plaque, and OPG deficient mice develop aortic calcification. To test whether OPG inhibits vascular calcification, we treated hyperlipidemic ldlr(−/−) mice on a high fat diet with Fc‐OPG or vehicle control. After 2 and 5 months, we assessed atherosclerotic lesion size and number, presence of aortic calcification, and osteogenic markers in aortic tissue. At 2 months, atherosclerotic lesion number was significantly reduced with Fc‐OPG treatment compared to control (0.03±0.02 vs. 0.07±0.05 lesions/mm media; p < 0.05), but lesion size and area were not different, suggesting that OPG may inhibit initiation, but not growth, of lesions. At 5 months, aortic calcification incidence, detected by von Kossa histochemical staining, was significantly decreased in mice treated with Fc‐OPG vs. vehicle control (4 of 14 vs. 11 of 17). Based on ELISA, osteocalcin, an osteogenic marker, was reduced by 72% in the aortas of OPG‐treated mice (8.3±10.3 vs. 29.3±25 ng/ml/mg total protein; p < 0.05). Expression of the other markers, msx2, runx2, and osterix mRNA, was not significantly different. These findings suggest that OPG may decrease osteogenic differentiation and mineralization in the artery wall. Supported in part by NIH grant HL/AR69261.