Periostin increased by mechanical stress upregulates interleukin‐6 expression in the ligamentum flavum
Periostin increased by mechanical stress upregulates interleukin‐6 expression in the ligamentum flavum
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DOI：
10.1096/fj.202200917rr
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发表时间：
2022-12
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通讯作者：
Akito Yabu;A. Suzuki;Kazunori Hayashi;Yusuke Hori;H. Terai;Kumi Orita;Hasibullah Habibi;Hamidullah Salimi;H. Kono;H. Toyoda;T. Maeno;S. Takahashi;K. Tamai;Tomonori Ozaki;Masayoshi Iwamae;Shoichiro Ohyama;Yuuki Imai;Hiroaki Nakamura
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作者：
Akito Yabu;A. Suzuki;Kazunori Hayashi;Yusuke Hori;H. Terai;Kumi Orita;Hasibullah Habibi;Hamidullah Salimi;H. Kono;H. Toyoda;T. Maeno;S. Takahashi;K. Tamai;Tomonori Ozaki;Masayoshi Iwamae;Shoichiro Ohyama;Yuuki Imai;Hiroaki Nakamura
黄韧带（LF）肥大是腰椎管狭窄的主要原因。尽管机械应力被认为是LF肥大的一个主要因素，但其导致肥大的确切机制尚未完全阐明。在这里，我们使用RNA - seq技术分析了兔LF肥大模型中长期机械应力导致的基因表达变化。结合先前报道的分析结果，确定了periostin是一种由于机械应力而表达波动的分子。利用人LF组织和原代LF细胞培养进一步研究了骨膜蛋白的表达和功能。骨膜蛋白在人肥大的LF组织中大量表达，且骨膜蛋白基因表达与LF厚度显著相关。在体外，机械应力增加了LF细胞中骨膜蛋白、转化生长因子- β1、α -平滑肌肌动蛋白、1型胶原α 1和白细胞介素- 6 （IL - 6）的基因表达。骨膜素阻断抑制了机械应力诱导的IL - 6基因表达，而骨膜素处理增加了IL - 6基因表达。我们的研究结果表明，机械应力上调骨膜蛋白，并通过上调IL - 6表达促进炎症，导致LF变性和肥大。骨膜蛋白可能是LF肥大的关键分子，也是腰椎管狭窄的治疗靶点。
Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long‐term mechanical stress were analyzed using RNA‐seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor‐β1, α‐smooth muscle actin, collagen type 1 alpha 1, and interleukin‐6 (IL‐6) in LF cells. Periostin blockade suppressed the mechanical stress‐induced gene expression of IL‐6 while periostin treatment increased IL‐6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL‐6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.