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 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.
Doehring
Lars Christian
LC
Medizinische Klinik II, Universitaetsklinikum Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany. Lars.Doehring@uk-sh.de
Heeger
Christian
C
Aherrahrou
Zouhair
Z
Kaczmarek
Piotr Maciel
PM
Erdmann
Jeanette
J
Schunkert
Heribert
H
Ehlers
Eva-Maria
EM
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology*; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000276:immunology; D018826:CD13 Antigens / Q000276:immunology*; D002114:Calcinosis / Q000276:immunology / Q000473:pathology; D054338:Cell Transdifferentiation / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053245:RANK Ligand / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D018183:Transplantation Chimera; D017539:Tunica Intima / Q000473:pathology*
D018952:Antigens, CD34; D053245:RANK Ligand; D011973:Receptors, LDL; C505689:Tnfsf11 protein, mouse; D018826:CD13 Antigens