Department of Anatomy, Shandong University School of Basic Medical Sciences, 44 Wenhua Xi Road, Jinan, 250012, Shandong Province, China.
Department of Orthopaedics, Shandong University Qilu Hospital, Jinan, 250012, China.
Skelet Muscle. 2018 Sep 15;8(1):29. doi: 10.1186/s13395-018-0175-9.
The formation of intrafusal muscle (IM) fibers and their contact with afferent proprioceptive axons is critical for construction, function, and maintenance of the stretch reflex. Many factors affect the formation of IM fibers. Finding new factors and mechanisms of IM fiber formation is essential for the reconstruction of stretch reflex arc after injury.
We established a coculture system of organotypic dorsal root ganglion (DRG) explants and dissociated skeletal muscle (SKM) cells. The formation of IM fibers was observed in this coculture system after neuregulin-1β (NRG-1β) incubation.
We found that NRG-1β promoted outgrowth of neurites and migration of neurons from the organotypic DRG explants and that this correlated with an induction of growth-associated protein 43 (GAP-43) expression. NRG-1β also increased the amount of nuclear bag fibers and nuclear chain fibers by elevating the proportion of tyrosine kinase receptor C (TrkC) phenotypic DRG neurons. In addition, we found that the effects of NRG-1β could be blocked by inhibiting ERK1/2, PI3K/Akt, and JAK2/STAT3 signaling pathways.
These data imply that NRG-1β promoted neurite outgrowth and neuronal migration from the organotypic DRG explants and that this correlated with an induction of GAP-43 expression. The modulating effects of NRG-1β on TrkC DRG neuronal phenotype may link to promote IM fiber formation. The effects produced by NRG-1β in this neuromuscular coculture system provide new data for the therapeutic potential on IM fiber formation after muscle injury.
肌梭内肌纤维（IM）的形成及其与传入本体感受轴突的接触对于牵张反射的构建、功能和维持至关重要。许多因素影响 IM 纤维的形成。寻找新的因素和 IM 纤维形成的机制对于损伤后牵张反射弧的重建至关重要。
我们建立了器官型背根神经节（DRG）外植体和分离的骨骼肌（SKM）细胞的共培养系统。在该共培养系统中孵育神经调节蛋白-1β（NRG-1β）后，观察 IM 纤维的形成。
我们发现 NRG-1β促进了器官型 DRG 外植体中神经突的生长和神经元的迁移，这与生长相关蛋白 43（GAP-43）表达的诱导相关。NRG-1β还通过提高酪氨酸激酶受体 C（TrkC）表型 DRG 神经元的比例，增加核袋纤维和核链纤维的数量。此外，我们发现 NRG-1β的作用可以通过抑制 ERK1/2、PI3K/Akt 和 JAK2/STAT3 信号通路来阻断。
这些数据表明，NRG-1β促进了器官型 DRG 外植体中神经突的生长和神经元的迁移，这与 GAP-43 表达的诱导相关。NRG-1β对 TrkC DRG 神经元表型的调节作用可能与促进 IM 纤维形成有关。NRG-1β在这种神经肌肉共培养系统中的作用为肌肉损伤后 IM 纤维形成的治疗潜力提供了新的数据。
