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首页> 外文期刊>Journal of Cellular Physiology >Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation
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Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation

机译:Hypomorphic条件删除E11 / Podoplanin揭示了一个骨细胞树突伸长的作用

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The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the initial stages of osteocyte differentiation. However, its precise function and regulatory mechanisms are still unknown. Due to the known embryonic lethality induced by global Pdpn deletion, we have herein explored the effect of bone-specific Pdpn knockdown on osteocyte form and function in the post-natal mouse. Extensive skeletal phenotyping of male and female 6-week-old Oc-cre; Pdpn(flox/flox) (cKO) mice and their Pdpn(flox/flox) controls (fl/fl) has revealed that Pdpn deletion significantly compromises tibial cortical bone microarchitecture in both sexes, albeit to different extents (p < 0.05). Consistent with this, we observed an increase in stiffness in female cKO mice in comparison to fl/fl mice (p < 0.01). Moreover, analysis of the osteocyte phenotype by phalloidin staining revealed a significant decrease in the dendrite volume (p < 0.001) and length (p < 0.001) in cKO mice in which deletion of Pdpn also modifies the bone anabolic loading response (p < 0.05) in comparison to age-matched fl/fl mice. Together, these data confirm a regulatory role for Pdpn in osteocyte dendrite formation and as such, in the control of osteocyte function. As the osteocyte dendritic network is known to play vital roles in regulating bone modeling/remodeling, this highlights an essential role for Pdpn in bone homeostasis.
机译:跨膜糖蛋白E11 / Podoplanin(Pdpn)与初始阶段骨细胞的分化。精确的函数和监管机制仍然未知。全球引起的致命性Pdpn删除,我们在此探索特异性的影响吗Pdpn击倒在骨细胞形成和功能产后鼠标。表现型的男性和女性流行Oc-cre;Pdpn(液氧/液氧)(cKO)老鼠和他们Pdpn(液氧/液氧)控制(fl / fl)显示Pdpn删除显著妥协胫骨骨密质微体系结构在两种性别,尽管不同的区段(p < 0.05)。与此一致的是,我们观察到的增加刚度在女性cKO老鼠相比fl / fl小鼠(p < 0.01)。骨细胞表型phalloidin染色在树突显示明显降低量(p < 0.001)和长度在cKO (p < 0.001)老鼠的删除Pdpn也修改了骨合成代谢加载响应(p < 0.05)相比同龄fl / fl老鼠。这些数据证实Pdpn的监管作用骨细胞树突的形成,因此,骨细胞功能的控制。树状网络中扮演重要的角色调节骨建模/重构,这在骨Pdpn突显出一个至关重要的角色体内平衡。

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