Estrogen depletion on In vivo osteocyte calcium signaling responses to mechanical loading.
Estrogen depletion on In vivo osteocyte calcium signaling responses to mechanical loading.
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DOI：
10.1016/j.bone.2021.116072
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发表时间：
2021-11
期刊：
影响因子：
4.1
通讯作者：
Schaffler MB
中科院分区：
文献类型：
--
作者：
Lewis KJ;Cabahug-Zuckerman P;Boorman-Padgett JF;Basta-Pljakic J;Louie J;Stephen S;Spray DC;Thi MM;Seref-Ferlengez Z;Majeska RJ;Weinbaum S;Schaffler MB
骨骼对机械刺激的微观结构适应会随着雌激素的缺乏而减弱。在这里，我们在小鼠体内测试了卵巢切除术（OVX）是否会改变骨细胞（骨骼的主要机械感觉细胞）对机械负荷的急性反应。我们还使用超分辨率显微镜（结构照明显微镜或 SIM）结合免疫组织化学来评估“骨细胞机械体”的数量和组织的变化，即 Panx1 通道、P2X7 受体和 CaV3 电压门控 Ca2+ 通道的复合物，聚集在骨细胞过程中 αvβ3 整合素焦点周围。将表达骨细胞靶向基因编码 Ca2+ 指示剂 (DMP1-GCaMP3) 的小鼠第三跖骨在体内循环加载至 250 至 3000 με 的菌株，并使用多光子显微镜评估中骨干中的骨细胞细胞内 Ca2+ 信号传导反应。对照小鼠中 Ca2+ 信号骨细胞的数量随着应变生理范围内施加的应变大小单调增加。 OVX 后 2 天，Ca2+ 信号骨细胞数量与负荷之间的关系没有变化。然而，在 OVX 后 28 天，它发生了显着改变。当负载高达 1000 με 时，响应（即 Ca2+ 信号）骨细胞的数量急剧减少；然而，在较高的品系中，Ca2+信号骨细胞的数量与对照小鼠相似。 OVX 显着改变了树突状过程中骨细胞机械体复合物的丰度、组成和组织。 OVX 后，也用 Panx 1、P2X7R 或 CaV3 染色的 αvβ3 灶的数量减少了近一半，表明随着雌激素的消耗，树突状突起上的骨细胞机械体损失。与此同时，其余焦点的 αvβ3 和通道蛋白染色面积显着增加，机械体成分的重新分布表明存在潜在的补偿反应。这些结果表明，雌激素消耗对骨骼机械适应的有害影响出现在机械感觉水平上。骨细胞失去感知微小（生理）机械刺激的能力。这种下降至少部分是由于骨细胞机械体结构和组织的变化造成的，这导致骨细胞（特别是其树突状突起）对机械刺激具有独特的敏感性。
Microstructural adaptation of bone in response to mechanical stimuli is diminished with estrogen deprivation. Here we tested in vivo whether ovariectomy (OVX) alters the acute response of osteocytes, the principal mechanosensory cells of bone, to mechanical loading in mice. We also used super resolution microscopy (Structured Illumination microscopy or SIM) in conjunction with immunohistochemistry to assess changes in the number and organization of “osteocyte mechanosomes” - complexes of Panx1 channels, P2X7 receptors and CaV3 voltage-gated Ca2+ channels clustered around αvβ3 integrin foci on osteocyte processes. Third metatarsals bones of mice expressing an osteocyte-targeted genetically encoded Ca2+ indicator (DMP1-GCaMP3) were cyclically loaded in vivo to strains from 250 to 3000 με and osteocyte intracellular Ca2+ signaling responses were assessed in mid-diaphyses using multiphoton microscopy. The number of Ca2+ signaling osteocytes in control mice increase monotonically with applied strain magnitude for the physiological range of strains. The relationship between the number of Ca2+ signaling osteocytes and loading was unchanged at 2 days post-OVX. However, it was altered markedly at 28 days post-OVX. At loads up to 1000 με, there was a dramatic reduction in number of responding (i.e. Ca2+ signaling) osteocytes; however, at higher strains the numbers of Ca2+ signaling osteocytes were similar to control mice. OVX significantly altered the abundance, make-up and organization of osteocyte mechanosome complexes on dendritic processes. Numbers of αvβ3 foci also staining with either Panx 1, P2X7R or CaV3 declined by nearly half after OVX, pointing to a loss of osteocyte mechanosomes on the dendritic processes with estrogen depletion. At the same time, the areas of the remaining foci that stained for αvβ3 and channel proteins increased significantly, a redistribution of mechanosome components suggesting a potential compensatory response. These results demonstrate that the deleterious effects of estrogen depletion on skeletal mechanical adaptation appear at the level of mechanosensation; osteocytes lose the ability to sense small (physiological) mechanical stimuli. This decline may result at least partly from changes in the structure and organization of osteocyte mechanosomes, which contribute to the distinctive sensitivity of osteocytes (particularly their dendritic processes) to mechanical stimulation.
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影响因子：
5.6
作者：
Banciu A;Banciu DD;Mustaciosu CC;Radu M;Cretoiu D;Xiao J;Cretoiu SM;Suciu N;Radu BM
通讯作者：
Radu BM
影响因子：
4.8
作者：
Aguirre, J. Ignacio;Plotkin, Lilian I.;Bellido, Teresita
通讯作者：
Bellido, Teresita
DOI：
10.1073/pnas.1009382107
发表时间：
2010-08-03
影响因子：
11.1
作者：
Burra, Sirisha;Nicolella, Daniel P.;Jiang, Jean X.
通讯作者：
Jiang, Jean X.
影响因子：
2.5
作者：
Bosch, Martha A.;Hou, Jingwen;Fang, Yuan;Kelly, Niartin J.;Ronnekleiv, Oline K.
通讯作者：
Ronnekleiv, Oline K.
影响因子：
--
作者：
Freitas-Andrade M;Bechberger JF;MacVicar BA;Viau V;Naus CC
通讯作者：
Naus CC