Potential involvement of semaphorin 3A in maintaining intervertebral disc tissue homeostasis
Potential involvement of semaphorin 3A in maintaining intervertebral disc tissue homeostasis
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DOI：
10.1002/jor.24258
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发表时间：
2019-04-01
影响因子：
2.8
通讯作者：
Fujita, Nobuyuki
中科院分区：
文献类型：
--
作者：
Mima, Yuichiro;Suzuki, Satoshi;Fujita, Nobuyuki
椎间盘是无血管的；然而，在退化的过程中，血管向外生长已被注意到。IVD变性中血管形成的机制尚不完全清楚。信号蛋白3A （Sema3A）最初被认为是发育中的神经系统生长轴突的化学排斥因子，可抑制血管生成。本研究旨在阐明Sema3A在无血管IVD中维持组织稳态的潜在作用。我们发现Sema3A mRNA在大鼠纤维环（AF）中的表达高于髓核（NP），且其表达水平随年龄的增长而下降。Sema3A的mRNA和蛋白表达水平在IVD变性大鼠AF组织中也被明显抑制。real-time RT-PCR和Western blot均清楚地表明，在大鼠AF细胞中，炎症因子处理显著降低了Sema3A的表达。在一项功能获得和功能丧失研究中，我们观察到Sema3A降低了大鼠心房颤动细胞的分解代谢转移。此外，我们的研究结果表明Sema3A可能抑制IL-6/JAK/STAT通路。最后，BrdU实验和成管实验显示，重组Sema3A处理能显著抑制HUVEC的增殖和成管。我们的研究结果表明Sema3A可能有助于维持IVD组织的稳态。因此，虽然需要进一步的研究，但Sema3A可能是抑制IVD变性的潜在分子靶点。(c) 2019年骨科研究学会。Wiley期刊公司出版。J骨科
Intervertebral discs (IVDs) are avascular; however, ingrowth of blood vessels into their outer regions has been noted during the progression of degeneration. The mechanisms underlying vascularization in IVD degeneration are not completely understood. Semaphorin 3A (Sema3A), originally characterized as a chemorepulsive factor for growing axons in the developing nervous system, inhibits angiogenesis. This study aimed to elucidate the potential involvement of Sema3A in maintaining tissue homeostasis within the avascular IVD. We demonstrated that the mRNA expression of Sema3A was higher in rat annulus fibrosus (AF) than in nucleus pulposus (NP) and that its expression level decreased with age. Both mRNA and protein expression level of Sema3A was also markedly suppressed in AF tissues of a rat IVD degeneration model. Both real-time RT-PCR and Western blot clearly indicated that Sema3A expression significantly reduced by treating inflammatory cytokines in rat AF cells. In a gain- and loss-of-function study, we observed that Sema3A reduced the catabolic shift in rat AF cells. In addition, our results indicated that Sema3A potentially inhibited the IL-6/JAK/STAT pathway. Finally, BrdU assay and tube formation assay revealed that treatment of recombinant Sema3A significantly blocks both proliferation and tube formation of HUVEC. Our results indicate that Sema3A may help maintain IVD tissue homeostasis. Thus, although further studies are needed, Sema3A may be a potential molecular target for suppressing IVD degeneration. (c) 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res