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Cited by 334

The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.

Inactivation of the Osteopontin Gene Enhances Vascular Calcification of Matrix Gla Protein–deficient Mice

Open access
Speer, Mei Y., McKee, Marc D., Guldberg, Robert E., Liaw, Lucy, Yang, Hsueh-Ying, Tung, Elyse, Karsenty, Gerard, Giachelli, Cecilia M.·2002·The Journal of Experimental Medicine

Abstract

Osteopontin (OPN) is abundantly expressed in human calcified arteries. To examine the role of OPN in vascular calcification, OPN mutant mice were crossed with matrix Gla protein (MGP) mutant mice. Mice deficient in MGP alone (MGP−/− OPN+/+) showed calcification of their arteries as early as 2 weeks (wk) after birth (0.33 ± 0.01 mmol/g dry weight), and the expression of OPN in the calcified arteries was greatly up-regulated compared with MGP wild-types. OPN accumulated adjacent to the mineral and colocalized to surrounding cells in the calcified media. Cells synthesizing OPN lacked smooth muscle (SM) lineage markers, SM α-actin and SM22α. However, most of them were not macrophages. Importantly, mice deficient in both MGP and OPN had twice as much arterial calcification as MGP−/− OPN+/+ at 2 wk, and over 3 times as much at 4 wk, suggesting an inhibitory effect of OPN in vascular calcification. Moreover, these mice died significantly earlier (4.4 ± 0.2 wk) than MGP−/− OPN+/+ counterparts (6.6 ± 1.0 wk). The cause of death in these animals was found to be vascular rupture followed by hemorrhage, most likely due to enhanced calcification. These studies are the first to demonstrate a role for OPN as an inducible inhibitor of ectopic calcification in vivo.

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Metadata

Authors
Speer, M. Y., McKee, M. D., Guldberg, R. E., Liaw, L., Yang, H.-Y., Tung, E., Karsenty, G., & Giachelli, C. M.
Venue
The Journal of Experimental Medicine
Published
2002-10-14
Volume
196
Issue
8
Pages
1047-1055
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2108152450
Cited by
334
References
51
FWCI
10.08
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Inactivation of the Osteopontin Gene Enhances Vascular Calcification of Matrix Gla Protein–deficient Mice. https://app.cochat.ai/papers/10.1084/jem.20020911
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Speer, M. Y., McKee, M. D., Guldberg, R. E., Liaw, L., Yang, H.-Y., Tung, E., Karsenty, G., & Giachelli, C. M. (2002). Inactivation of the Osteopontin Gene Enhances Vascular Calcification of Matrix Gla Protein–deficient Mice. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20020911

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