Alendronate affects cartilage resorption by regulating vascular endothelial growth factor expression in rats.
This study was performed to determine effects of alendronate on the tibial proximal epiphyseal cartilage undergoing endochondral ossification and the expression of vascular endothelial growth factor (VEGF) from the cartilage. Alendronate was injected subcutaneously every other day in postnatal Day 1 Sprague Dawley rats. The rats were sacrificed 3, 5, 7, and 10 days after the first injection. The effect of alendronate treatment for 10 days was demonstrated from the morphological change that the area of the secondary ossification center in the epiphysis was significantly smaller in the alendronate group than that in the control group (P < 0.05). Strong immunoreactivity to VEGF was observed in the hypertrophied chondrocytes and some proliferating chondrocytes in the epiphyseal cartilage at postnatal Day 5 and was decreased after the alendronate treatment for 5 days. Immunoreactivity was observed in not only hypertrophied cells but also the peripheral cartilaginous matrix adjacent to the vascular canals invading into the central portion of the cartilage at postnatal Day 7. This reactivity was also reduced considerably by the alendronate treatment for 7 days. The level of VEGF expression was reduced by the alendronate treatment at both the transcription and translation levels. However, the transcriptional level of the flt-1 and flk-1 receptors was relatively unaltered by the treatment. These results suggest that VEGF expression is required for vascular invasion into the developing cartilage and alendronate can affect its resorption by downregulating VEGF expression.
Kang
J H
JH
Dental Science Research Institute, Second Stage Brain Korea, School of Dentistry, Chonnam National University, Gwangju, South Korea.
Choi
N K
NK
Kang
S J
SJ
Yang
S Y
SY
Ko
H M
HM
Jung
J Y
JY
Kim
M S
MS
Koh
J T
JT
Kim
W J
WJ
Oh
W M
WM
Kim
B Y
BY
Kim
S H
SH
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001808:Blood Vessels / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006132:Growth Plate / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D006984:Hypertrophy / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects* / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000187:drug effects / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000187:drug effects / Q000378:metabolism
D050071:Bone Density Conservation Agents; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D019386:Alendronate