Journal
DEVELOPMENTAL BIOLOGY
Volume 332, Issue 2, Pages 196-211Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2009.05.552
Keywords
Cartilage; Perichondrium; Endochondral bone formation; VEGF-A; Perichondrial angiogenesis; Anti-angiogenic properties
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Funding
- Ministry of Education, Culture, Sport, Science and Technology of Japan
- Tanabe Medical Frontier Conference
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During endochondral bone formation, vascular invasion initiates the replacement of avascular cartilage by bone. We demonstrate herein that the cartilage-specific overexpression of VEGF-A(164) in mice results in the hypervascularization of soft connective tissues away from cartilage. Unexpectedly, perichondrial tissue remained avascular in addition to cartilage. Hypervascularization of tissues similarly occurred when various VEGF-A isoforms were overexpressed in the chick forelimb, but also in this case perichondrial tissue and cartilage were completely devoid of vasculature. However, following bony collar formation, anti-angiogenic properties in perichondrial tissue were lost and perichondrial angiogenesis was accelerated by VEGF-A(146), VEGF-A(166), or VEGF-A(190). Once the perichondrium was vascularized, osteoclast precursors were recruited from the circulation and the induction of MMP9 and MMP13 can be observed in parallel with the activation of TGF-beta signaling. Neither perichondrial angiogenesis nor the subsequent cartilage vascularization was found to be accelerated by the non-heparin-binding VEGF-A(122) or by the VEGF-A(166)Delta E-162-R-166 mutant lacking a neuropilin-binding motif. Hence, perichondrial angiogenesis is a prerequisite for subsequent cartilage vascularization and is differentially regulated by VEGF-A isoforms. (C) 2009 Elsevier Inc. All rights reserved.
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