The peripheral nervous system and focal bony erosions in arthritis

感觉神经和交感神经支配骨，它们的神经纤维在正常情况下有两种不同的作用。一方面，它们向大脑传递机械、热和化学刺激（传入功能）。另一方面，它们是骨稳态（传出功能）所必需的外周营养因子和抗营养因子的来源。两位申请者将他们在炎症神经免疫学和软骨/骨研究方面的活动结合起来，研究关节炎局灶性骨侵蚀背景下的神经系统（这是一个未知领域）。在spp1468的背景下，第一个应用主要是针对交感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）。它包括调查可能的炎症诱导交感神经支配从肾上腺素能表型向胆碱能表型的转变（交感神经转变）。在本提案的功能部分，神经递质受体和神经递质对骨髓源性破骨细胞的影响在正常和关节炎动物进行了研究。这些研究将是后续项目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SPP 1468 -免疫骨，从而引起对骨稳态重要调节因子的研究。从长远来看，申请者期望从神经-骨免疫学领域获得新的关节炎治疗靶点。

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.