Introduction: Recent studies have elucidated that C-type natriuretic peptide (CNP), a member of natriuretic peptide family, is a potent stimulator of endochondral bone growth; CNP and its membranous guanylyl cyclase receptor, GC-B are expressed in growth plate, and mice with targeted overexpression of CNP in growth plate exhibit prominent skeletal overgrowth, whereas CNP or GC-B knockout mice develop severely short stature phenotype owing to their impaired endochondral bone growth. We are trying to translate the strong stimulatory effect of CNP on bone growth into a medical treatment for patients with skeletal dysplasia, a group of genetic disorders characterized by disturbances in skeletal development. In the present study, we performed systemic administration of CNP to mice model of achondroplasia, the most common form of skeletal dysplasia.
Methods and results: We performed continuous i.v. administration of CNP to 3-week-old achondroplastic model mice for 4 weeks, and investigated the effects on their impaired skeletal growth. CNP stimulated the longitudinal growth of achondroplastic model mice dose-dependently, and the naso-anal length of achondroplastic mice treated with CNP at the dose of 1 μg/kg per min was almost comparable to that of wild-type mice treated with vehicle. CNP administration at the dose of 0.1 μg/kg per min considerably recovered the impaired growth of long bones in achondroplastic mice, and at the dose of 1 μg/kg per min, some bones grew rather longer than those in wild-type mice treated with vehicle. Histological examination revealed that narrowed growth plate observed in achondroplastic mice was recovered by administration of 1 μg/kg per min CNP to the extent of wild-type growth plate treated with vehicle.
Conclusion: We demonstrated that systemic administration of CNP is effective for the recovery of impaired skeletal growth in mice model of achondroplasia. Systemic administration of CNP is a potential therapeutic strategy for the treatment of skeletal dysplasia including achondroplasia.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
05 - 09 May 2012
European Society of Endocrinology