Intermittent PTH (1-34) injection rescues the retarded skeletal development and postnatal lethality of mice mimicking human achondroplasia and thanatophoric dysplasia

• DOI: 10.1093/hmg/dds181
• Publication Date: 2012-05-26T00:30:17Z
• Authors: Y. Xie; N. Su; M. Jin; H. Qi; J. Yang; C. Li; X. Du; F. Luo; B. Chen; Y. Shen; H. Huang; C. J. Xian; C. Deng; L. Chen
• Keywords: Achondroplasia; Dwarfism; Bone Growth; Osteopenia; Osteochondrodysplasia; Long bone

Achondroplasia (ACH) and thanatophoric dysplasia (TD) are caused by gain-of-function mutations of fibroblast growth factor receptor 3 (FGFR3) they the most common forms dwarfism lethal dwarfism, respectively. Currently, there few effective treatments for ACH. For neonatal lethality TD patients, no practical therapies available. We here showed that systemic intermittent PTH (1-34) injection can rescue phenotype type II (TDII) mice significantly alleviate retarded skeleton development ACH mice. PTH-treated had longer naso-anal length than control mice, bone lengths humeri tibiae were rescued to be comparable with those wild-type Our study also found premature fusion cranial synchondroses in was partially corrected after treatment, suggesting treatment may progressive narrowing neurocentral cannot readily surgery. In addition, we improve osteopenia structure The increased expression PTHrP down-regulated FGFR3 level responsible positive effects on TDII