Laser irradiation decreases sclerostin expression in bone and osteogenic cells
Laser irradiation decreases sclerostin expression in bone and osteogenic cells
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DOI：
10.1096/fj.202001032r
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发表时间：
2020-08
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影响因子：
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通讯作者：
Yujin Ohsugi;Sayaka Katagiri;T. Hirota;Hiromi Niimi;Masahiro Hatasa;Kazuki Watanabe;Tsuyoshi Shimohira;K. Mizutani;Moe Kitazawa;Ayumi Matsuzawa;H. Kadokura;S. Yokose;T. Iwata;A. Aoki
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作者：
Yujin Ohsugi;Sayaka Katagiri;T. Hirota;Hiromi Niimi;Masahiro Hatasa;Kazuki Watanabe;Tsuyoshi Shimohira;K. Mizutani;Moe Kitazawa;Ayumi Matsuzawa;H. Kadokura;S. Yokose;T. Iwata;A. Aoki
抗sclerostin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。激光照射引发各种效应，包括生物刺激，可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，以阐明激光消融骨中更好的骨愈合机制。在这里，我们评估了Er：YAG激光消融、钻取和未处理对照骨中的全面和连续基因表达，发现激光照射抑制了骨中的Sost（编码蛋白：sclerostin）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，序列微阵列分析显示，骨消融后24小时，钻削骨和激光消融骨之间的基因表达模式明显不同。Hippo信号通路显著富集，而炎症相关通路在激光消融后6小时未受影响，表明激光照射引起机械刺激。仅钻取骨在24小时时显示出丰富的炎症相关基因集和途径，而激光消融骨中没有。我们的研究表明，激光照射可能成为骨质疏松症的一种新的治疗方式，通过抑制sclerostin的表达，而不诱导炎症。
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.