title: Vascularization of primary and secondary ossification centres in the human growth plate.
abstract: BACKGROUND
  The switch from cartilage template to bone during endochondral ossification of the growth plate requires a dynamic and close interaction between cartilage and the developing vasculature. Vascular invasion of the primarily avascular hypertrophic chondrocyte zone brings chondroclasts, osteoblast- and endothelial precursor cells into future centres of ossification.Vascularization of human growth plates of polydactylic digits was studied by immunohistochemistry, confocal-laser-scanning-microscopy and RT-qPCR using markers specific for endothelial cells CD34 and CD31, smooth muscle cells α-SMA, endothelial progenitor cells CD133, CXCR4, VEGFR-2 and mesenchymal progenitor cells CD90 and CD105. In addition, morphometric analysis was performed to quantify RUNX2+ and DLX5+ hypertrophic chondrocytes, RANK+ chondro- and osteoclasts, and CD133+ progenitors in different zones of the growth plate.
  
  
  RESULTS
  New vessels in ossification centres were formed by sprouting of CD34+ endothelial cells that did not co-express the mature endothelial cell marker CD31. These immature vessels in the growth plate showed no abluminal coverage with α-SMA+ smooth muscle cells, but in their close proximity single CD133+ precursor cells were found that did not express VEGFR-2, a marker for endothelial lineage commitment. In periosteum and in the perichondrial groove of Ranvier that harboured CD90+/CD105+ chondro-progenitors, in contrast, mature vessels were found stabilized by α-SMA+ smooth muscle cells.
  
  
  CONCLUSIONS
  Vascularization of ossification centres of the growth plate was mediated by sprouting of capillaries coming from the bone collar or by intussusception rather than by de-novo vessel formation involving endothelial progenitor cells. Vascular invasion of the joint anlage was temporally delayed compared to the surrounding joint tissue.
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Walzer
authors.forename: Erdal
authors.initials: E
authors.lastname: Cetin
authors.forename: Ruth
authors.initials: R
authors.lastname: Grübl-Barabas
authors.forename: Irene
authors.initials: I
authors.lastname: Sulzbacher
authors.forename: Beate
authors.initials: B
authors.lastname: Rueger
authors.forename: Werner
authors.initials: W
authors.lastname: Girsch
authors.forename: Stefan
authors.initials: S
authors.lastname: Toegel
authors.forename: Reinhard
authors.initials: R
authors.lastname: Windhager
authors.affiliation: Clinic for Blood Group Serology and Transfusion Medicine, Waeringer Guertel 18-20, Vienna, 1090, Austria. michael.b.fischer@meduniwien.ac.at.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fischer
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D002675:Child, Preschool; D019902:Chondrocytes / Q000378:metabolism; D005260:Female; D006132:Growth Plate / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D017689:Polydactyly / Q000235:genetics / Q000601:surgery*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D014157:Transcription Factors