A soluble activin type IIA receptor induces bone formation and improves skeletal integrity
A soluble activin type IIA receptor induces bone formation and improves skeletal integrity
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DOI：
10.1073/pnas.0711263105
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发表时间：
2008-05-13
影响因子：
11.1
通讯作者：
Bouxsein, Mary L.
中科院分区：
文献类型：
--
作者：
Pearsall, R. Scott;Canalis, Ernesto;Bouxsein, Mary L.
影响骨周转调节的疾病可能会导致骨骼脆性和骨折风险增加。研究表明，转化生长因子-β超家族成员参与了骨量的调节。激活素A是一种转化生长因子-β信号转导配体，在骨组织中含量较高，可能在骨代谢调节中发挥作用。在这里，我们证明了通过激活素的高亲和力受体，II型激活素受体(ActRIIA)的配体信号的药物阻断，通过给药融合到小鼠IgG2a-Fc的ActRIIA的可溶胞外域，增加了正常小鼠和已确定骨质丢失的卵巢切除小鼠的骨形成、骨量和骨强度。这些观察结果支持开发这一治疗骨骼脆性疾病的药理策略。
Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-beta superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-beta signaling ligand, is present at high levels in bone and may play a role in the regulation of bone metabolism. Here we demonstrate that pharmacological blockade of ligand signaling through the high affinity receptor for activin, type II activin receptor (ActRIIA), by administration of the soluble extracellular domain of ActRIIA fused to a murine IgG2a-Fc, increases bone formation, bone mass, and bone strength in normal mice and in ovariectomized mice with established bone loss. These observations support the development of this pharmacological strategy for the treatment of diseases with skeletal fragility.