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

Lars Christian Doehring, Christian Heeger, Zouhair Aherrahrou, Piotr Maciel Kaczmarek, Jeanette Erdmann, Heribert Schunkert, Eva Maria Ehlers

25 Citations (Scopus)


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. Chondrocytelike 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 Sm22α, 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.

Original languageEnglish
JournalAmerican Journal of Pathology
Issue number1
Pages (from-to)473-480
Number of pages8
Publication statusPublished - 01.01.2010


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