Kokubu Naoki, Tsujii Masaya, Akeda Koji, Iino Takahiro, Sudo Akihiro
Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu, Japan.
J Orthop Surg (Hong Kong). 2018 May-Aug;26(3):2309499018812953. doi: 10.1177/2309499018812953.
: To determine the expression and distribution of bone morphogenetic protein (BMP)-7 and related molecules during peripheral nerve regeneration and to assess whether administration of parathyroid hormone (PTH) drug (1-34) potentiates the intrinsic upregulation of BMP-7/Smad signaling.
: The rat sciatic nerves were crushed with an aneurysm clip resulting in axonal degeneration. In the normal nerve, and at 1, 2, 4, and 8 weeks after injury, BMP-7, BMP receptors, p-Smad 1/5/8, and Noggin, the endogenous BMP antagonist, were evaluated. Additionally, the distribution of BMP-7 was assessed by fluorescent double immunostaining. In vitro studies were also performed to examine the effect of BMP-7 and PTH (1-34) administration on rat Schwann cells (SCs).
: Aneurysm clip made reliable animal model of the nerve injury with recovery at 8 weeks after the injury. BMP-7/Smad protein and mRNA were significantly upregulated on axon-SCs units at 1 week after injury, and this upregulated expression was maintained for 4 weeks. Besides, significant upregulation of Noggin's expression was observed on axon-SCs units at 2 weeks after injury. Moreover, fluorescent double immunostaining showed co-localization between expression of BMP-7 and p75NTR during axonal regeneration. In the in vitro study, administration of BMP-7 induced significant proliferation of SCs. Application of PTH (1-34) upregulated BMP-7 on SCs.
DISCUSSION/CONCLUSION:: BMPs were reported to be involved in protection and recovery after injury as well as in neurogenesis. Our current study showed that BMP/Smad signaling molecules were upregulated on dedifferentiated SCs after peripheral nerve injury and that administration of BMP-7 increased SC viability in vitro. These results suggested that axonal regeneration could be induced via upregulation of endogenous BMP-7 on SCs by PTH (1-34) administration.
确定骨形态发生蛋白（BMP）-7及相关分子在周围神经再生过程中的表达和分布，并评估甲状旁腺激素（PTH）药物（1-34）的给药是否能增强BMP-7/Smad信号通路的内源性上调。
用动脉瘤夹夹闭大鼠坐骨神经导致轴突变性。在正常神经以及损伤后1、2、4和8周，评估BMP-7、BMP受体、p-Smad 1/5/8和内源性BMP拮抗剂Noggin。此外，通过荧光双重免疫染色评估BMP-7的分布。还进行了体外研究以检查BMP-7和PTH（1-34）给药对大鼠雪旺细胞（SCs）的影响。
动脉瘤夹制作了可靠的神经损伤动物模型，损伤后8周恢复。损伤后1周，轴突-SCs单位上的BMP-7/Smad蛋白和mRNA显著上调，且这种上调表达持续4周。此外，损伤后2周，轴突-SCs单位上观察到Noggin表达显著上调。而且，荧光双重免疫染色显示轴突再生过程中BMP-7表达与p75NTR共定位。在体外研究中，BMP-7给药诱导SCs显著增殖。PTH（1-34）应用上调SCs上的BMP-7。
讨论/结论：据报道，BMP参与损伤后的保护和恢复以及神经发生。我们目前的研究表明，周围神经损伤后去分化的SCs上BMP/Smad信号分子上调，且BMP-7给药增加体外SCs活力。这些结果表明，通过PTH（1-34）给药上调SCs上的内源性BMP-7可诱导轴突再生。
