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.
复制标题
C 型利钠肽可在酶替代疗法下恢复粘多糖贮积症 VII 小鼠的生长障碍。
作者：
T. Yamashita;T. Fujii;I. Yamauchi;Y. Ueda;Keisho Hirota;Y. Kanai;A. Yasoda;N. Inagaki
粘多糖病（mps）的生长损伤是一个尚未解决的问题，因为它对酶替代疗法（ERT）和生长激素治疗具有抗性。c型利钠肽（CNP）是一种很有前途的促生长药物。在这里，我们使用Gusbmps-2J小鼠（MPS型Ⅶ模型），通过流体动力基因传递CNP和ERT联合治疗，研究CNP对MPS生长损伤的影响。虽然单一治疗不足以恢复治疗小鼠的矮小身材，但联合治疗可成功恢复。CNP和ERT不仅在骨骼生长中有协同作用，而且在生长板中也有协同作用。ERT通过加速细胞增殖或抑制细胞凋亡，减少静息区细胞肿胀，增加细胞数量。CNP增厚了增生带和肥厚带。对于骨的变化，ERT通过减少骨形成和增加骨吸收来恢复骨硬化，而CNP对这一过程没有不利影响。此外，通过关节间隙和关节软骨的分析，建议ERT改善关节变形。CNP与ERT联合使用可修复MPSⅦ小鼠的矮小身材，改善生长板和骨代谢的异常。
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 stature of MPS Ⅶ mice in combination with ERT which improved abnormalities of growth plates and bone metabolism.
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影响因子：
15.9
作者：
Bartolomeo, Rosa;Cinque, Laura;Settembre, Carmine
通讯作者：
Settembre, Carmine
新生肝基因治疗后粘多糖贮积症VII小鼠疾病病理表现的评估。
DOI：
10.1006/mthe.2002.0809
发表时间：
2002
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Xu,Lingfei;Mango,RobertL;Sands,MarkS;Haskins,MarkE;Ellinwood,NMatthew;Ponder,KatherineParker
通讯作者：
Ponder,KatherineParker
影响因子：
3.8
作者：
Xing, Elizabeth M.;Wu, Susan;Ponder, Katherine P.
通讯作者：
Ponder, Katherine P.
影响因子：
5.8
作者：
Munoz-Calvo, Maria T.;Barrios, Vicente;Argente, Jesus
通讯作者：
Argente, Jesus