[Effect of the regulation of IGFs system components in retinoic acid-induced congenital clubfoot].
The fetal rat models with congenital clubfoot were constructed by treating 24 Wistar rats with all trans retinoic acid (ATRA). The MC-3T3-E1 cells were cultured with ATRA, 17 beta-estrogen (E2) or combinations of the two chemicals. The flow cytometer was used to determine the cell proliferation. The insulin-like growth factor-II (IGF-II ) and IGF conjugated protein-6 (IGFBP-6) mRNA level in rat calvaria bone tissue and MC-3T3-E1 cells were detected by northern blotting analysis and reverse transcription polymerase chain reaction. The congenital clubfoot of fetal rat was induced by ATRA in concentration of 100 approximately 140 mg/kg with dosage-dependence effect. The expression of IGF-II mRNA and cell proliferation were enhanced by E2(1 x 10(-6) mol/L) in rat calvaria bone tissue and MC-3T3-E1 cells, whereas the IGFBP-6 mRNA was increased. ATRA(1 x 10(-6) mol/L), however, inhibited the effect of E2 on regulation of IGF- II gene and IGFBP-6 gene as well as MC-3T3-E1 cell proliferation. These findings provide the evidence that ATRA can induce congenital skeleton malformation and congenital clubfoot in pregnant Wistar rats. IGF-II and IGFBP-6 are important regulative factors for skeleton development and osteoblast proliferation in rat.
Guo
Lei
L
Department of Orthopedic Surgery, First Clinical College, China Medical University, Shenyang 110001, China.
Zhao
Yan-Yan
YY
Ji
Shi-Jun
SJ
Sun
Kai-Lai
KL
Dong
Ling-Yue
LY
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003025:Clubfoot / Q000139:chemically induced*; D005260:Female; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014212:Tretinoin / Q000633:toxicity*
D018976:Insulin-Like Growth Factor Binding Protein 6; D012333:RNA, Messenger; D014212:Tretinoin; D007335:Insulin-Like Growth Factor II