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Am J Pathol. 2010 Jul;177(1):473-80. doi: 10.2353/ajpath.2010.090758. Epub 2010 May 20.

Myeloid CD34+CD13+ precursor cells transdifferentiate into chondrocyte-like cells in atherosclerotic intimal calcification.

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1
Medizinische Klinik II, Universitaetsklinikum Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany. Lars.Doehring@uk-sh.de

Abstract

Chondrogenic differentiation is pivotal in the active regulation of artery calcification. We investigated the cellular origin of chondrocyte-like cells in atherosclerotic intimal calcification of C57BL/6 LDLr(-/-) mice using bone marrow transplantation to trace ROSA26-LacZ-labeled cells. Immunohistochemical costaining of collagen type II with LacZ and leukocyte defining surface antigens was performed and analyzed by high-resolution confocal microscopy. Chondrocyte-like cells were detected in medium and advanced atherosclerotic plaques accounting for 7.1 +/- 1.6% and 14.1 +/- 1.7% of the total plaque cellularity, respectively. Chimera analysis exhibited a mean of 89.8% LacZ(+) cells in peripheral blood and collagen type II costaining with LcZ revealed an average 88.8 +/- 7.6% cytoplasmatic LacZ(+) evidence within the chondrocyte-like cells. To examine whether hematopoietic stem cells contribute to the phenotype, stem cell marker CD34 and myeloid progenitor-associated antigen CD13 were analyzed. CD34(+) was detectable in 86.9 +/- 8.1% and CD13(+) evidence in 54.2 +/- 7.6% of chondrocyte-like cells, attributable most likely because of loss of surface markers during transdifferentiation. Chondrocyte differentiation factor Sox-9 was detected in association with chondrocyte-like cells, whereas Sm22alpha, a marker for smooth muscle cells, could not be demonstrated. The results show that the majority of chondrocyte-like cells were of bone marrow origin, whereas CD34(+)/CD13(+) myeloid precursors appeared to infiltrate the plaque actively and transdifferentiated into chondrocytes-like cells in the progression of atherosclerosis.

PMID:
20489139
PMCID:
PMC2893689
DOI:
10.2353/ajpath.2010.090758
[Indexed for MEDLINE]
Free PMC Article
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