挽救肌浆网Ca2+-ATP酶2泵功能缺陷：改善2型糖尿病骨机械反应性的新方法。
Rescuing SERCA2 pump deficiency: A novel approach to improve bone mechano-responsiveness in type 2 diabetes.
作者信息
Yu Zhifeng, Guo X Edward
机构信息
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, USA.
出版信息
Mechanobiol Med. 2024 Feb 24;2(2):100047. doi: 10.1016/j.mbm.2024.100047. eCollection 2024 Jun.
A recent study published in demonstrated that restoring SERCA2 pump deficiency can enhance bone mechano-responsiveness in type 2 diabetes (T2D) by modulating osteocyte calcium dynamics. The findings revealed that in T2D mice, the ability of the bone to respond to mechanical stress is compromised, primarily due to attenuated calcium oscillatory dynamics within osteocytes rather than in osteoblasts or osteoclasts. The underlying mechanism of this reduction in bone mechano-responsiveness in T2D was identified as a specific decrease in osteocytic SERCA2 expression mediated by PPARα. Additionally, mice overexpressing SERCA2 in osteocytes exhibited reduced deterioration of bone mechano-responsiveness induced by T2D. Collectively, this study provides mechanistic insights into T2D-induced deterioration in bone mechano-responsiveness and identifies a promising therapeutic approach to counteract T2D-associated fragility fractures.
最近发表的一项研究表明，恢复肌浆网钙ATP酶2（SERCA2）泵缺陷可通过调节骨细胞钙动力学来增强2型糖尿病（T2D）患者的骨机械反应性。研究结果显示，在T2D小鼠中，骨骼对机械应力的反应能力受损，这主要是由于骨细胞内而非成骨细胞或破骨细胞内的钙振荡动力学减弱所致。T2D患者骨机械反应性降低的潜在机制被确定为过氧化物酶体增殖物激活受体α（PPARα）介导的骨细胞SERCA2表达特异性降低。此外，在骨细胞中过表达SERCA2的小鼠表现出由T2D诱导的骨机械反应性恶化减轻。总的来说，这项研究为T2D诱导的骨机械反应性恶化提供了机制性见解，并确定了一种有前景的治疗方法来对抗T2D相关的脆性骨折。
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