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Laser irradiation decreases sclerostin expression in bone and osteogenic cells
The FASEB Journal ( IF 4.4 ) Pub Date : 2020-08-05 , DOI: 10.1096/fj.202001032r
Yujin Ohsugi 1 , Sayaka Katagiri 1 , Tomomitsu Hirota 2 , Hiromi Niimi 1 , Masahiro Hatasa 1 , Kazuki Watanabe 1 , Tsuyoshi Shimohira 1 , Koji Mizutani 1 , Moe Kitazawa 3 , Ayumi Matsuzawa 3 , Hiroshi Kadokura 4 , Satoshi Yokose 4 , Takanori Iwata 1 , Akira Aoki 1
Affiliation  

Anti‐sclerostin monoclonal antibody romosozumab, a treatment for osteoporosis, reduced vertebral fracture risk and clinical fracture. Laser irradiation triggers various effects, including bio‐stimulation, which can induce beneficial therapeutic effects and biological responses. Originally, we performed in vivo experiments to clarify the mechanism of better bone healing in laser‐ablated bone. Here, we evaluated comprehensive and sequential gene expression in Er:YAG laser‐ablated, bur‐drilled, and nontreated control bones, and found laser irradiation suppressed Sost (coding protein: sclerostin) expression in the bone, possibly via stimulation of mechanotransducers. Surprisingly, bio‐stimulation effect of laser suppressed Sost expression in the primary osteogenic cells. Decreased sclerostin expression after laser irradiation was also validated both in vivo and in vitro. In addition, sequential microarray analysis revealed that the gene expression pattern was clearly different at 24 hours after bone ablation between bur‐drilled and laser‐ablated bones. The Hippo signaling pathway was significantly enriched, whereas inflammation‐related pathways were not affected at 6 hours after the laser ablation, indicating that laser irradiation caused mechanical stimulation. Only bur‐drilled bone showed enriched inflammation‐related gene sets and pathways at 24 hours, not in the laser‐ablated bone. Our study suggests that laser irradiation may become a new treatment modality for osteoporosis, by inhibiting sclerostin expression without inducing inflammation.

中文翻译:

激光照射降低骨和成骨细胞中硬化蛋白的表达

抗硬化素单克隆抗体 romosozumab,治疗骨质疏松症,降低椎骨骨折风险和临床骨折。激光照射会触发各种效应,包括生物刺激,可以诱导有益的治疗效果和生物反应。最初,我们进行了体内实验以阐明激光烧蚀骨中更好的骨愈合机制。在这里,我们评估了 Er:YAG 激光烧蚀、钻孔和未处理的对照骨骼中全面和连续的基因表达,发现激光照射抑制了骨骼中的 Sost(编码蛋白:硬化蛋白)表达,可能是通过刺激机械换能器。令人惊讶的是,激光的生物刺激作用抑制了原代成骨细胞中的 Sost 表达。在体内和体外也验证了激光照射后硬化蛋白表达的降低。此外,连续微阵列分析显示,在骨消融后 24 小时,钻孔和激光消融骨之间的基因表达模式明显不同。Hippo 信号通路显着富集,而炎症相关通路在激光消融后 6 小时未受到影响,表明激光照射引起了机械刺激。只有 bur 钻骨在 24 小时时显示出丰富的炎症相关基因集和通路,而不是在激光烧蚀骨中。我们的研究表明,通过抑制硬化蛋白表达而不引起炎症,激光照射可能成为骨质疏松症的一种新治疗方式。连续微阵列分析显示,在骨消融后 24 小时,钻孔和激光消融骨之间的基因表达模式明显不同。Hippo 信号通路显着富集,而炎症相关通路在激光消融后 6 小时未受到影响,表明激光照射引起了机械刺激。只有 bur 钻骨在 24 小时时显示出丰富的炎症相关基因集和通路,而不是在激光烧蚀骨中。我们的研究表明,通过抑制硬化蛋白表达而不引起炎症,激光照射可能成为骨质疏松症的一种新治疗方式。连续微阵列分析显示,在骨消融后 24 小时,钻孔和激光消融骨之间的基因表达模式明显不同。Hippo 信号通路显着富集,而炎症相关通路在激光消融后 6 小时未受到影响,表明激光照射引起了机械刺激。只有 bur 钻骨在 24 小时时显示出丰富的炎症相关基因集和通路,而不是在激光烧蚀骨中。我们的研究表明,通过抑制硬化蛋白表达而不引起炎症,激光照射可能成为骨质疏松症的一种新治疗方式。Hippo 信号通路显着富集,而炎症相关通路在激光消融后 6 小时未受到影响,表明激光照射引起了机械刺激。只有 bur 钻骨在 24 小时时显示出丰富的炎症相关基因集和通路,而不是在激光烧蚀骨中。我们的研究表明,通过抑制硬化蛋白表达而不引起炎症,激光照射可能成为骨质疏松症的一种新治疗方式。Hippo 信号通路显着富集,而炎症相关通路在激光消融后 6 小时未受到影响,表明激光照射引起了机械刺激。只有 bur 钻骨在 24 小时时显示出丰富的炎症相关基因集和通路,而不是在激光烧蚀骨中。我们的研究表明,通过抑制硬化蛋白表达而不引起炎症,激光照射可能成为骨质疏松症的一种新治疗方式。
更新日期:2020-08-05
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