Changes in the intra- and peri-cellular sclerostin distribution in lacuno-canalicular system induced by mechanical unloading
Changes in the intra- and peri-cellular sclerostin distribution in lacuno-canalicular system induced by mechanical unloading
复制标题
机械卸载引起的腔隙小管系统细胞内和细胞周硬化素分布的变化
DOI：
10.1007/s00774-020-01135-9
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发表时间：
2020
影响因子：
3.3
通讯作者：
Kamioka Hiroshi
中科院分区：
文献类型：
--
作者：
Osumi Ryuta;Wang Ziyi;Ishihara Yoshihito;Odagaki Naoya;Iimura Tadahiro;Kamioka Hiroshi
骨形成的负调控因子Sclerostin（Scl）在骨细胞中的表达受机械刺激的调控。然而，详细的Scl在骨细胞中的分布，以响应机械卸载仍不清楚。切除右侧坐骨神经和股神经作为机械去负荷治疗。在左侧进行假手术。神经创伤后一周，通过外周定量计算机断层扫描评估股骨的骨密度，并在股骨干的冠状面进行免疫荧光检查。分析Scl从骨髓到骨膜侧的平均荧光强度和荧光分布，以估计Scl表达并确定Scl响应于机械卸载而优选分布到哪一侧（骨髓或骨膜）。结果在股骨远端干骺端，神经创伤引起的机械去负荷使骨密度显著降低，使Scl分布更靠近前内侧骨髓，而Scl表达仅在外侧增加。TEM结果表明，只有Scl在小管的表达增加，由mechanicalunloading.ConclusionsOur结果表明，即使是短期的机械卸载是足以降低骨密度，和机械卸载不仅调节Scl的表达，但也改变了Scl在骨细胞网络和亚细胞结构的分布。
IntroductionMechanical stimuli regulate Sclerostin (Scl), a negative regulator of bone formation, expression in osteocytes. However, the detailed Scl distribution in osteocytes in response to mechanical unloading remains unclear.Materials and methodsTwelve-week-old male rats were used. The sciatic and femoral nerves on the right side were excised as mechanical unloading treatment. A sham operation was performed on the left side. One week after neurotrauma, the bone density of the femora was evaluated by peripheral quantitative computed tomography, and immunofluorescence was performed in coronal sections of the femoral diaphysis. The mean fluorescence intensity and fluorescent profile of Scl from the marrow to the periosteal side were analyzed to estimate the Scl expression and determine to which side (marrow or periosteal) the Scl prefers to distribute in response to mechanical unloading. The most sensitive region indicated by the immunofluorescence results was further investigated by transmission electron microscopy (TEM) with immunogold staining to show the Scl expression changes in different subcellular structures.ResultsIn femur distal metaphysis, neurotrauma-induced mechanical unloading significantly decreased the bone density, made the distribution of Scl closer to the marrow on the anterior and medial side, and increased the Scl expression only on the lateral side. TEM findings showed that only the expression of Scl in canaliculi was increased by mechanical unloading.ConclusionsOur results showed that even short-term mechanical unloading is enough to decrease bone density, and mechanical unloading not only regulated the Scl expression but also changed the Scl distribution in both the osteocyte network and subcellular structures.