[Effect of the regulation of IGFs system components in retinoic acid-induced congenital clubfoot].

ABSTRACT

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.