Vascularization of primary and secondary ossification centres in the human growth plate

• Published in: BMC developmental biology 2014-08, Vol.14 (1), p.36-36, Article 36
• Main Authors: Walzer, Sonja M, Cetin, Erdal, Grübl-Barabas, Ruth, Sulzbacher, Irene, Rueger, Beate, Girsch, Werner, Toegel, Stefan, Windhager, Reinhard, Fischer, Michael B
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Calcification; Cell Differentiation; Cells, Cultured; Child, Preschool; Chondrocytes - metabolism; Colleges & universities; Design; Endothelium; Experiments; Extracellular matrix; Female; Genetic aspects; Growth; Growth Plate - physiology; Human growth; Humans; Infant; Infant, Newborn; Male; Neovascularization, Physiologic; Osteogenesis; Polydactyly - genetics; Polydactyly - surgery; Smooth muscle; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Vascular endothelial growth factor
• ISSN: 1471-213X; 1471-213X
• DOI: 10.1186/s12861-014-0036-7

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. 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. 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.