Bone Deterioration in Response to Chronic High-Altitude Hypoxia Is Attenuated by a Pulsed Electromagnetic Field Via the Primary Cilium/HIF-1α Axis
Bone Deterioration in Response to Chronic High-Altitude Hypoxia Is Attenuated by a Pulsed Electromagnetic Field Via the Primary Cilium/HIF-1α Axis
复制标题
脉冲电磁场通过初级纤毛/HIF-1α轴减轻慢性高原缺氧引起的骨退化
DOI：
10.1002/jbmr.4772
复制
发表时间：
2023-02-13
影响因子：
6.2
通讯作者：
Jing, Da
中科院分区：
文献类型：
--
作者：
Hao, Xiaoxia;Wang, Dan;Jing, Da
慢性高海拔缺氧在多种生物体中引起不可逆的异常。新出现的证据表明，低气压缺氧明显抑制骨量和骨强度。然而，很少有有效的方法被确定来防止这种骨缺损。在这里，我们评估了脉冲电磁场（pemf）在无创抵抗低气压缺氧引起的骨退化方面的潜力。我们观察到，15 Hz和20高斯（Gs）的外源性PEMF处理通过主要调节成骨细胞和成骨细胞介导的骨形成活性，改善了模拟海拔4500米的低气压缺氧慢性暴露6周的大鼠的松质和皮质骨量、骨微观结构和骨骼力学性能。此外，我们的研究结果表明，尽管PEMF在体外缺氧培养中刺激了原代成骨细胞的功能活性，但它对缺氧条件下的破骨细胞和骨细胞的影响可以忽略不计。在机械上，初级纤毛被发现在暴露于缺氧的成骨细胞中起主要的电磁传感器的作用。多囊素PC-1/PC-2复合体被认为是缺氧暴露成骨细胞初级纤毛中的初级钙通道，负责检测外部PEMF信号，从而将这些生物物理信号转化为细胞内生化事件，包括细胞内可溶性腺苷环化酶（sAC）表达的显著增加和随后的环磷酸腺苷（cAMP）浓度的升高。第二信使cAMP抑制氧稳态相关的缺氧诱导因子1- α (HIF-1 α)的转录，从而促进成骨细胞分化，改善骨表型。综上所述，本研究不仅提高了我们对高海拔地区骨生理学的认识，更重要的是，提出了一种无创、经济有效的方法来改善高海拔地区骨质流失。(c) 2023美国骨与矿物研究学会（ASBMR）。
Chronic high-altitude hypoxia induces irreversible abnormalities in various organisms. Emerging evidence indicates that hypobaric hypoxia markedly suppresses bone mass and bone strength. However, few effective means have been identified to prevent such bone deficits. Here, we assessed the potential of pulsed electromagnetic fields (PEMFs) to noninvasively resist bone deterioration induced by hypobaric hypoxia. We observed that exogenous PEMF treatment at 15 Hz and 20 Gauss (Gs) improved the cancellous and cortical bone mass, bone microstructure, and skeletal mechano-properties in rats subjected to chronic exposure of hypobaric hypoxia simulating an altitude of 4500 m for 6 weeks by primarily modulating osteoblasts and osteoblast-mediated bone-forming activity. Moreover, our results showed that whereas PEMF stimulated the functional activity of primary osteoblasts in hypoxic culture in vitro, it had negligible effects on osteoclasts and osteocytes exposed to hypoxia. Mechanistically, the primary cilium was found to function as the major electromagnetic sensor in osteoblasts exposed to hypoxia. The polycystins PC-1/PC-2 complex was identified as the primary calcium channel in the primary cilium of hypoxia-exposed osteoblastic cells responsible for the detection of external PEMF signals, and thereby translated these biophysical signals into intracellular biochemical events involving significant increase in the intracellular soluble adenylyl cyclase (sAC) expression and subsequent elevation of cyclic adenosine monophosphate (cAMP) concentration. The second messenger cAMP inhibited the transcription of oxygen homeostasis-related hypoxia-inducible factor 1-alpha (HIF-1 alpha), and thus enhanced osteoblast differentiation and improved bone phenotype. Overall, the present study not only advances our understanding of bone physiology at high altitudes, but more importantly, proposes effective means to ameliorate high altitude-induced bone loss in a noninvasive and cost-effective manner. (c) 2023 American Society for Bone and Mineral Research (ASBMR).