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.
