Dissociation of bone resorption and bone formation in adult mice with a non-functional V-ATPase in osteoclasts leads to increased bone strength.
Dissociation of bone resorption and bone formation in adult mice with a non-functional V-ATPase in osteoclasts leads to increased bone strength.
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DOI：
10.1371/journal.pone.0027482
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Richter J
中科院分区：
文献类型：
--
作者：
Henriksen K;Flores C;Thomsen JS;Brüel AM;Thudium CS;Neutzsky-Wulff AV;Langenbach GE;Sims N;Askmyr M;Martin TJ;Everts V;Karsdal MA;Richter J
破骨细胞分泌酸缺陷引起的骨化症，以骨吸收缺陷、破骨细胞数量增多、骨形成正常或增多为特征。相比之下，骨骼的质量很差，尽管形成和吸收是分离的。为了阐明去偶联对成年小鼠骨骼强度的影响，我们将来自对照组或oc/oc小鼠的造血干细胞移植到受辐射的三个月大的正常小鼠身上，并对它们进行了12到28周的跟踪。通过外周血流式细胞仪检测植入水平。每6周采集一次血清样本，用于骨转换标志物的测定。在终止时收集骨骼进行微CT和机械测试。获得了98%的植入率。从第6周到终止，骨吸收显著减少，而与对照组相比，破骨细胞数量增加。骨形成在第6周增加，第12周恢复正常，以后减少。股骨和椎骨的微CT和力学分析显示皮质骨和松质骨的骨体积和骨强度增加。综上所述，这些数据表明，成年小鼠的酸分泌减弱会导致解偶联，并提高骨骼强度。
Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption. To shed light on the effect of uncoupling in adult mice with respect to bone strength, we transplanted irradiated three-month old normal mice with hematopoietic stem cells from control or oc/oc mice, which have defective acid secretion, and followed them for 12 to 28 weeks. Engraftment levels were assessed by flow cytometry of peripheral blood. Serum samples were collected every six weeks for measurement of bone turnover markers. At termination bones were collected for µCT and mechanical testing. An engraftment level of 98% was obtained. From week 6 until termination bone resorption was significantly reduced, while the osteoclast number was increased when comparing oc/oc to controls. Bone formation was elevated at week 6, normalized at week 12, and reduced onwards. µCT and mechanical analyses of femurs and vertebrae showed increased bone volume and bone strength of cortical and trabecular bone. In conclusion, these data show that attenuation of acid secretion in adult mice leads to uncoupling and improves bone strength.
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