Role of oncostatin M in the nervous systems

肿瘤抑素M(OSM)是白介素6(IL-6)细胞因子家族中的一员，参与最终的造血、肝脏发育和局部炎症。然而，人们对OSM在神经系统中的作用知之甚少。原位杂交显示，嗅球星形胶质细胞、脉络丛上皮细胞和软膜脑膜细胞均有OSM受体β的表达。该基因在胚胎14.5天首次在舌下核的大神经元中表达，并一直持续到新生的小鼠。OSMR基因和蛋白主要定位于发育中的舌下神经核腹侧亚核，在成年背根神经节(DRGs)，OSMR仅在小神经元中表达。约28%的OSMR阳性神经元含有TrkA免疫反应(-ir)，63%表达Ret-ir。神经元内不含P物质和降钙素基因相关肽等神经肽。此外，所有OSMR阳性神经元都表达香草素受体1(TRPV1)和P2X3嘌呤能受体。在OSM缺陷小鼠的DRG中，TRPV1和P2X3阳性的小型神经元明显减少。在急性热痛、机械痛、化学痛和内脏痛模型中，OSM缺陷小鼠的毒害反应显著减少。因此，OSM在背根节伤害性感觉神经元的亚型发育过程中起着至关重要的作用。关于发育中和成年小鼠背根神经节中TRPV2阳性神经元对神经营养因子的依赖性，我们知之甚少。TRPV2是。当TRPV1和TRPM8还未检测到时，第一次在E 11.5的DRG神经元表达。TrkC在E11.5和E13.5的大多数TRPV2阳性的DRG神经元中表达。在成年背根神经节中，TrkC和Ret分别在68%和25%的TRPV2阳性神经元中表达。这些结果表明，在整个发育过程中，TRPV2主要在依赖NT-3的DRG神经元亚群中表达，在成年小鼠中也是如此。

Oncostatin M(OSM) is a member of the interleukin(IL)-6 cytokine family, which is involved in definitive hematopoiesis, the development of liver, and local inflammation. However, little is known about the role of OSM in the nervous system. In situ hybridization shows that OSM receptor β (OSMR) mRNA was found in astrocytes of olfactory bulb, epithelial cells of choroid plexus, and meningeal cells in pia mater. Its gene expression was first observed in large neurons of the hypoglossal nucleus at embryonic day (E) 14.5, which was sustained until neonatal mice. OSMR mRNA and protein were mainly localized in the ventral subnucleus of the developing hypoglossal nucleus.In the adult dorsal root ganglia (DRGs), OSMR was exclusively expressed in small-sized neurons. Approximately 28% of OSMR-positive neurons contained TrkA-immunoreactivity (-ir), 63% expressed Ret-ir. No neuropeptides, including substance P and calcitonin gene-related peptide, were contained in the neurons. Furthermore, all OSMR-positive neurons expressed both vanilloid receptor 1(TRPV1) and P2X3 purinergic receptor.In the DRGs of the OSM-deficient mice, TRPV1- and P2X3-positive small-sized neurons were significantly decreased. OSM-deficient mice displayed significantly reduced noxious responses in models of acute thermal, mechanical, chemical, and visceral pain. Thus, OSM plays an essential role in the development of a subtype of nociceptive neurons in the DRGs.Little is known about the neurotrophin dependence of TRPV2-positive neurons in the developing and adult DRGs of mice. TRPV2 was. first expressed in DRG neurons at E 11.5, when neither TRPV1 nor TRPM8 were detected yet. TrkC was expressed in most of TRPV2-positive DRG neurons at E11.5 and E13.5. In adult DRGs, TrkC and Ret were expressed in 68% and 25% of TRPV2-positive neurons, respectively. These results suggest that TRPV2 is expressed predominantly in the NT-3-dependent subpopulation of DRG neurons throughout the development and in adult mice.