The peripheral nervous system and focal bony erosions in arthritis

感觉神经和交感神经支配骨骼，它们的神经纤维在正常情况下有两种不同的作用。一方面，它们将机械、热和化学刺激传递到大脑(传入功能)。另一方面，它们是骨内稳态(传出功能)所必需的外周营养因子和抗营养因子的来源。这两位申请者结合了他们在炎症神经免疫学和软骨/骨骼研究方面的活动，在关节炎局部骨质侵蚀的背景下研究神经系统(这是隐蔽的Terra)。在SPP 1468的上下文中的第一个应用主要针对交感神经和感觉神经支配的描述以及关节炎局灶性骨侵蚀中神经递质阳性的细胞(研究平台)。它包括炎症诱导的交感神经在炎症中从肾上腺素能向胆碱能表型转变的可能的研究(交感神经转变)。在这项建议的功能部分，研究了正常动物和关节炎动物的神经递质受体和神经递质对骨髓来源的破骨细胞的影响。这些研究将是后续项目中进一步功能研究的起点。我们的项目将神经纤维和神经递质引入到SPP1468-免疫球蛋白中，从而引发了对骨骼稳态的重要调节因素的研究。从长远来看，申请者期待神经骨免疫学领域出现新的治疗关节炎的靶点。

Sensory and sympathetic nerves innervate bone, and their nerve fibers have two different roles in the normal situation. On one side, they transmit mechanical, thermal, and chemical stimuli to the brain (afferent function). On the other side, they are source of peripheral trophic and anti–trophic factors essential for bone homeostasis (efferent function). The two applicants combine their activities in neuroimmunology of inflammation and cartilage / bone research to study the nervous system in the context of focal bony erosions in arthritis (this is terra incognita ). The first application in the context of the SPP 1468 is mainly directed towards the description of sympathetic and sensory innervation and of cells positive for neurotransmitters in focal bony erosions in arthritis (the platform for the research). It includes the investigation of a possible inflammation–induced shift of sympathetic innervation from the adrenergic to the cholinergic phenotype in inflammation (sympathetic transition). In the functional part of this proposal, neurotransmitter receptors and effects of neurotransmitters on bone marrow– derived osteoclasts are investigated in normal and arthritic animals. These studies will be a starting point for further functional studies in follow-up projects. Our project introduces nerve fibers and neurotransmitters into the SPP 1468 – Immunobone, thus, giving rise to studies on important regulators of bone homeostasis. In the long run, the applicants expect new therapeutic arthritis targets from the field of neuro–osteoimmunology.