Hypoxia inhibits the growth, differentiation and bone-forming capacity of rat osteoblasts
Hypoxia inhibits the growth, differentiation and bone-forming capacity of rat osteoblasts
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DOI：
10.1016/j.yexcr.2006.02.007
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发表时间：
2006-06-10
影响因子：
3.7
通讯作者：
Arnett, T. R.
中科院分区：
文献类型：
--
作者：
Utting, J. C.;Robins, S. P.;Arnett, T. R.
我们研究了低氧对长期原代培养的大鼠成骨细胞功能的影响。Po(2)从20%降至5%和2%，矿化骨结节的形成分别减少1.7倍和11倍。当Po(2)进一步降至0.2%时，骨结节的形成几乎消失。通过(3)H-胸腺嘧啶核苷掺入法检测，缺氧抑制骨形成的部分原因是成骨细胞增殖减少。低氧还显著降低成骨细胞碱性磷酸酶(ALP)的活性和表达。碱性磷酸酶和骨钙素的mRNAs的表达，提示向成骨表型分化的抑制。缺氧。不能增加成骨细胞的凋亡率，但可引起可逆性的静止状态。透射电子显微镜显示，在2%O(2)中培养的成骨细胞所沉积的胶原纤维比在20%O(2)中培养的成骨细胞沉积的胶原纤维更少、更少。此外，低氧成骨细胞产生的胶原含有较低比例的羟赖氨酸残基，并对胃酶降解表现出更高的敏感性。这些数据证明了成骨细胞对成功骨形成的绝对需氧量，并强调了血管系统在维持骨健康中的重要性。我们最近发现，缺氧也是破骨细胞形成的有力刺激因素。综合考虑，我们的结果有助于解释发生在骨折、肿瘤、炎症和感染部位以及患有血管疾病或贫血的个体的骨丢失。(C)2006 Elsevier Inc.保留所有权利。
We investigated the effect of hypoxia on rat osteoblast function in long-term primary cultures. Reduction of pO(2) from 20% to 5% and 2% decreased formation of mineralized bone nodules 1.7-fold and 11-fold, respectively. When pO(2) was reduced further to 0.2%, bone nodule formation was almost abolished. The inhibitory effect of hypoxia on bone formation was partly due to decreased osteoblast proliferation, as measured by (3)H-thymidine incorporation. Hypoxia also sharply reduced osteoblast alkaline phosphatase (ALP) activity and expression. of mRNAs for ALP and osteocalcin, suggesting inhibition of differentiation to the osteogenic phenotype. Hypoxia. did not increase the apoptosis of osteoblasts but induced a reversible state of quiescence. Transmission electron microscopy revealed that Collagen fibrils deposited by osteoblasts cultured in 2% O(2) were less organized and much less abundant than in 20% O(2) cultures. Furthermore, collagen produced by hypoxic osteoblasts contained a lower percentage of hydroxylysine residues and exhibited an increased sensitivity to pepsin degradation. These data demonstrate the absolute oxygen requirement of osteoblasts for successful bone formation and emphasize the importance of the vasculature in maintaining bone health. We recently showed that hypoxia also acts in a reciprocal manner as a powerful stimulator of osteoclast formation. Considered together, our results help to explain the bone loss that occurs at the sites of fracture, tumors, inflammation and infection, and in individuals with vascular disease or anemia. (c) 2006 Elsevier Inc. All rights reserved.