Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs.
Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs.
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DOI：
10.1038/ncomms12503
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发表时间：
2016-08-16
影响因子：
16.6
通讯作者：
Asahara H
中科院分区：
文献类型：
--
作者：
Nakamichi R;Ito Y;Inui M;Onizuka N;Kayama T;Kataoka K;Suzuki H;Mori M;Inagawa M;Ichinose S;Lotz MK;Sakai D;Masuda K;Ozaki T;Asahara H
椎间盘（IVD）突出的主要发病机制涉及衰老或过度机械应力引起的纤维环（AF）破坏以及由此导致的髓核脱垂。由于 IVD 的无血管性质以及缺乏对维持 IVD 的机制的了解，目前的疗法不会导致组织再生。在这里，我们证明同源盒蛋白 Mohawk (Mkx) 是调节 AF 发育、维持和再生的关键转录因子。 Mkx 主要在人和小鼠的外 AF (OAF) 中表达。在 Mkx−/− 小鼠中，与野生型相比，OAF 显示出多个肌腱/韧带相关基因的缺陷、OAF 胶原纤维直径更小以及 IVD 变性进展更快。过度表达 Mkx 的间充质干细胞可促进小鼠 AF 缺损模型中的功能性 AF 再生，并形成丰富的胶原纤维。我们的结果表明了房颤再生的治疗策略。 同源框蛋白 Mohwak (Mkx) 参与肌腱和韧带的发育。在这里，作者表明，椎间盘外纤维环中的 Mkx 在维持 IVD 中发挥着作用，表明过度表达 Mkx 的干细胞可增强小鼠的治疗性 IVD 再生。
The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx−/− mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration. Homeobox protein Mohwak (Mkx) is involved in tendon and ligament development. Here the authors show that Mkx in the outer annulus fibrosus of the intervertebral disc plays a role in maintenance of the IVD, showing that stem cells overexpressing Mkx enhance therapeutic IVD regeneration in mice.