Inhibiting Activin-A Signaling Stimulates Bone Formation and Prevents Cancer-Induced Bone Destruction In Vivo
Inhibiting Activin-A Signaling Stimulates Bone Formation and Prevents Cancer-Induced Bone Destruction In Vivo
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DOI：
10.1002/jbmr.142
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发表时间：
2010-12-01
影响因子：
6.2
通讯作者：
Croucher, Peter
中科院分区：
文献类型：
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作者：
Chantry, Andrew D.;Heath, Debby;Croucher, Peter
在骨中生长的癌症，如骨髓瘤和乳腺癌转移，引起破坏性的溶骨性骨破坏。这些癌症通过刺激骨细胞骨吸收和抑制骨形成来劫持骨重塑。目前，治疗的主要目标是阻断骨吸收，但这种方法只取得了有限的成功刺激成骨细胞骨形成以促进修复是一种新的替代方法我们表明可溶性激活素Ⅱ A型受体融合蛋白（ActRIIA muFc）刺激成骨细胞生成（p <0.01），促进骨形成（p <0.01）和增加体内骨量（p <0.01）。我们表明，在携带小鼠骨髓瘤细胞的小鼠中，溶骨性骨病变的发展是由骨吸收增加（p <0.05）和骨形成抑制（p <0.01）引起的。ActRIIA muFc处理刺激成骨细胞生成（p <0.01），防止骨髓瘤诱导的骨形成抑制（p <0.05），阻断溶骨性骨病变的发展（p <0.05），并增加存活（p <0.05）。我们还显示，在乳腺癌骨转移的鼠模型中，这些发现表明，用ActRIIA muFc刺激成骨细胞骨形成阻断了骨髓瘤和乳腺癌模型中溶骨性骨病变和骨转移的形成，并为治疗癌症的这种衰弱方面的新方法铺平了道路（C）。2010年美国骨与矿物质研究学会
Cancers that grow in bone, such as myeloma and breast cancer metastases, cause devastating osteolytic bone destruction These cancers hijack bone remodeling by stimulating osteoclastic bone resorption and suppressing bone formation Currently, treatment is targeted primarily at blocking bone resorption, but this approach has achieved only limited success Stimulating osteoblastic bone formation to promote repair is a novel alternative approach We show that a soluble activin receptor type IIA fusion protein (ActRIIA muFc) stimulates osteoblastogenesis (p < 01), promotes bone formation (p < 01) and increases bone mass in vivo (p < 001) We show that the development of osteolytic bone lesions in mice bearing murine myeloma cells is caused by both increased resorption (p < 05) and suppression of bone formation (p < 01) ActRIIA muFc treatment stimulates osteoblastogenesis (p < 01), prevents myeloma-induced suppression of bone formation (p < 05), blocks the development of osteolytic bone lesions (p < 05), and increases survival (p < 05) We also show, in a murine model of breast cancer bone metastasis, that ActRIIA muFc again prevents bone destruction (p < 001) and inhibits bone metastases (p < 05) These findings show that stimulating osteoblastic bone formation with ActRIIA muFc blocks the formation of osteolytic bone lesions and bone metastases in models of myeloma and breast cancer and paves the way for new approaches to treating this debilitating aspect of cancer (C) 2010 American Society for Bone and Mineral Research