Prenatal muscle forces are necessary for vertebral segmentation and disc structure, but not for notochord involution in mice.
Prenatal muscle forces are necessary for vertebral segmentation and disc structure, but not for notochord involution in mice.
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DOI：
10.22203/ecm.v041a36
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发表时间：
2021-05-22
影响因子：
3.1
通讯作者：
Nowlan NC
中科院分区：
文献类型：
--
作者：
Levillain A;Ahmed S;Kaimaki DM;Schuler S;Barros S;Labonte D;Iatridis JC;Nowlan NC
胚胎肌力是正常椎体发育和脊柱弯曲所必需的，但它们在椎间盘（IVD）发育中的作用尚不清楚。当前研究的目的是确定肌肉收缩如何影响(1)脊索内陷和椎体分割，以及(2)IVD的发展，包括机械特性和形态，以及纤维环中的胶原纤维排列。在三个产前阶段采集肌肉发育不良（mdg）小鼠：在Theiler期（TS）22时脊髓复旧开始，在TS24时复旧完成，在TS27时形成IVD。椎体和IVD的发展是通过组织学、免疫荧光和压痕测试来表征的。结果显示，在TS22和TS24之间，脊索复清和椎体分割独立于肌肉收缩发生。然而，在没有肌肉收缩的情况下，我们发现TS27颈椎区椎体融合，同时伴有(i)髓核向背侧移位，（ii）纤维环胶原结构排列破坏，以及（iii）纤维环粘性行为增加。这些发现强调了机械力在IVD发育过程中的重要作用，并证明了肌肉负荷在发育过程中对纤维环形成的关键作用。他们进一步提出，在制造纤维增强组织工程替代IVD作为IVD退行性变的治疗方法时，需要机械载荷。
Embryonic muscle forces are necessary for normal vertebral development and spinal curvature, but their involvement in intervertebral disc (IVD) development remains unclear. The aim of the current study was to determine how muscle contractions affect (1) notochord involution and vertebral segmentation, and (2) IVD development including the mechanical properties and morphology, as well as collagen fibre alignment in the annulus fibrosus. Muscular dysgenesis (mdg) mice were harvested at three prenatal stages: at Theiler Stage (TS)22 when notochord involution starts, at TS24 when involution is complete, and at TS27 when the IVD is formed. Vertebral and IVD development were characterised using histology, immunofluorescence, and indentation testing. The results revealed that notochord involution and vertebral segmentation occurred independently of muscle contractions between TS22 and TS24. However, in the absence of muscle contractions, we found vertebral fusion in the cervical region at TS27, along with (i) a displacement of the nucleus pulposus towards the dorsal side, (ii) a disruption of the structural arrangement of collagen in the annulus fibrosus, and (iii) an increase in viscous behaviour of the annulus fibrosus. These findings emphasise the important role of mechanical forces during IVD development, and demonstrate a critical role of muscle loading during development to enable proper annulus fibrosus formation. They further suggest a need for mechanical loading in the creation of fibre-reinforced tissue engineering replacement IVDs as a therapy for IVD degeneration.