The potential role of VEGF-induced vascularisation in the bony repair of injured growth plate cartilage.
Growth plate injuries often result in undesirable bony repair causing bone growth defects, for which the underlying mechanisms are unclear. Whilst the key importance of pro-angiogenic vascular endothelial growth factor (VEGF) is well-known in bone development and fracture repair, its role during growth plate bony repair remains unexplored. Using a rat tibial growth plate injury repair model with anti-VEGF antibody, Bevacizumab, as a single i.p. injection (2.5 mg/kg) after injury, this study examined the roles of VEGF-driven angiogenesis during growth plate bony repair. Histology analyses observed isolectin-B4-positive endothelial cells and blood vessel-like structures within the injury site on days 6 and 14, with anti-VEGF treatment significantly decreasing blood-vessel-like structures within the injury site (P<0.05). Compared with untreated controls, anti-VEGF treatment resulted in an increase in undifferentiated mesenchymal repair tissue, but decreased bony tissue at the injury site at day 14 (P<0.01). Consistently, microcomputed tomography analysis of the injury site showed significantly decreased bony repair tissue after treatment (P<0.01). RT-PCR analyses revealed a significant decrease in osteocalcin (P<0.01) and a decreasing trend in Runx2 expression at the injury site following treatment. Furthermore, growth plate injury-induced reduced tibial lengthening was more pronounced in anti-VEGF-treated injured rats on day 60, consistent with the observation of a significantly increased height of the hypertrophic zone adjacent to the growth plate injury site (P<0.05). These results indicate that VEGF is important for angiogenesis and formation of bony repair tissue at the growth plate injury site as well as for endochondral bone lengthening function of the uninjured growth plate.
School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, City East Campus, GPO Box 2471, Adelaide, South Australia 5001, Australia Department of Orthopaedic Surgery, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia.
Rosa
R
Chung
Bruce K
BK
Foster
Cory J
CJ
Xian
D000818:Animals; D002356:Cartilage / Q000098:blood supply* / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D006132:Growth Plate / Q000098:blood supply* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009389:Neovascularization, Pathologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072042:Salter-Harris Fractures; D013977:Tibia / Q000098:blood supply / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014945:Wound Healing
D042461:Vascular Endothelial Growth Factor A
VEGF; angiogenesis; bony repair; growth plate injury