Vascularization of primary and secondary ossification centres in the human growth plate
1 Department of Orthopaedics, Karl Chiari Lab for Orthopaedic Biology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria
2 Department of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria
3 Clinic for Blood Group Serology and Transfusion Medicine, Waeringer Guertel 18-20, Vienna, 1090, Austria
4 Department of Pediatric Orthopaedics, Orthopaedic Hospital Speising, Speisinger Strasse 109, Vienna, 1130, Austria
5 Department for Health Sciences and Biomedicine, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, Krems, 3500, Austria
BMC Developmental Biology 2014, 14:36 doi:10.1186/s12861-014-0036-7Published: 28 August 2014
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 ?-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.
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 ?-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 ?-SMA+ smooth muscle cells.
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.