Molecular basis on bone growth disturbance : Novel treatment for achondroplasia

点击翻译按钮获取中文摘要

Achondroplasia (ACH) is the most common form of genetic short statue. Recently we treat them with human growth hormone but its effect is limited. To explore new therapeutic applications, we performed PTH treatment for ACH model mouse (AchTG).[Short-term-trial] Wild (WT) and AchTG were treated with daily PTH subcutaneous injection (100μ/kg,1000μ/kg or vehicle) during day 7 to 20, then at day 21, their femurs were dissected, measured their length and analyzed histologically. [Long-term-trial] WT and AchTG mouse were treated with 3-times/week PTH subcutaneous injection (100μ/kg) during 1^<st> to 5^<th> week, then at day 42, their femurs, tibias, radiuses and humeruses were dissected, measured their length and analyzed histologically.AchTG femurs were significantly disturbed in longitudinal bone growth compared with WT ones. PTH significantly improved bone growth of AchTG but of WT. Histologically, PTH expands growth plate in both AchTG and WT femurs in short-term-trial but in long-term-trial.We confirmed that constitutive active FGFR3 mutation suppressed bone growth in transgenic mice and that PTH rescued bone from the growth disturbance. Our results suggest that PTH has potential to rescue the bone growth disturbance in achondroplasia.