Myeloid CD34+ CD13+ Precursor Cells Transdifferentiate into Chondrocyte-Like Cells in Atherosclerotic Intimal Calcification

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 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.