Department of Biomedicine, Aarhus University, Aarhus, Denmark; Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark; Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
Bone. 2018 May;110:326-334. doi: 10.1016/j.bone.2018.02.026. Epub 2018 Feb 28.
Disuse causes a rapid and substantial bone loss distinct in its pathophysiology from the bone loss associated with cancers, age, and menopause. While inhibitors of the activin-receptor signaling pathway (IASPs) have been shown to prevent ovariectomy- and cancer-induced bone loss, their application in a model of disuse osteopenia remains to be tested. Here, we show that a soluble activin type IIA receptor (ActRIIA-mFc) increases diaphyseal bone strength and cancellous bone mass, and mitigates the loss of femoral neck bone strength in the Botulinum Toxin A (BTX)-model of disuse osteopenia in female C57BL/6J mice. We show that ActRIIA-mFc treatment preferentially stimulates a dual-effect (anabolic-antiresorptive) on the periosteal envelope of diaphyseal bone, demonstrating in detail the effects of ActRIIA-mFc on cortical bone. These observations constitute a previously undescribed feature of IASPs that mediates at least part of their ability to mitigate detrimental effects of unloading on bone tissue. The study findings support the application of IASPs as a strategy to combat bone loss during disuse.
废用会导致快速而大量的骨质流失，其病理生理学与癌症、年龄和绝经相关的骨质流失明显不同。虽然激活素受体信号通路抑制剂 (IASPs) 已被证明可预防卵巢切除术和癌症引起的骨质流失，但它们在废用性骨质疏松症模型中的应用仍有待测试。在这里，我们表明，一种可溶性激活素 IIA 型受体 (ActRIIA-mFc) 可增加骨干的骨强度和松质骨量，并减轻女性 C57BL/6J 小鼠中肉毒杆菌毒素 A (BTX) 废用性骨质疏松症模型中股骨颈骨强度的丧失。我们表明，ActRIIA-mFc 治疗优先刺激骨干骨外骨膜的双重效应（合成代谢-抗吸收），详细说明了 ActRIIA-mFc 对皮质骨的影响。这些观察结果构成了 IASPs 的一个以前未描述的特征，介导了它们至少部分减轻骨组织卸载不利影响的能力。该研究结果支持将 IASPs 作为一种策略应用于治疗废用性骨丢失。
