C-type natriuretic peptide restores growth impairment under enzyme replacement in mice with mucopolysaccharidosis VII.

C-type natriuretic peptide restores growth impairment under enzyme replacement in mice with mucopolysaccharidosis VII. Endocrinology. 2020 Jan 24;: Authors: Yamashita T, Fujii T, Yamauchi I, Ueda Y, Hirota K, Kanai Y, Yasoda A, Inagaki N Abstract Growth impairment in mucopolysaccharidoses (MPSs) is an unresolved issue as it is resistant to enzyme replacement therapy (ERT) and growth hormone therapy. C-type natriuretic peptide (CNP) is a promising agent that has growth promoting effects. Here, we investigate the effects of CNP on growth impairment of MPSs using Gusbmps-2J mice, a model for MPS type Ⅶ, with combination therapy of CNP and ERT by hydrodynamic gene delivery. Although monotherapies were not sufficient to restore short statures of treated mice, combination therapy resulted in successful restoration. The synergistic effects of CNP and ERT were not only observed in skeletal growth but also in growth plates. ERT reduced cell swelling in the resting zone and increased cell number by accelerating proliferation or inhibiting apoptosis. CNP thickened the proliferative and hypertrophic zones. Regarding changes in the bone, ERT restored bone sclerosis through decreased bone formation and increased bone resorption, and CNP did not adversely affect this process. In addition, improvement of joint deformation by ERT was suggested by analyses of joint spaces and articular cartilage. CNP additively provided restoration of the short stat...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research