6. Osteoclast progenitors induce catecholaminergic-to-cholinergic transition of sympathetic nerve fibers under healthy conditions

Abstract

Sympathetic nerve fibers innervate bone and tissue adjacent to joints. They play an important role in bone and tissue homeostasis. Under certain conditions, sympathetic nerve fibers can change their phenotype from catecholaminergic to cholinergic. This can be important because anti-inflammatory effects of acetylcholine have been described (alpha-7-nicotinic receptor). We asked whether this transition might occur in the joint during collagen-induced arthritis (CIA) in mice or during rheumatoid arthritis (RA) and osteoarthritis (OA) in humans. Sections of limbs from 30 immunized mice and synovial tissue samples obtained from 30 OA and 12 RA patients were stained for tyrosine hydroxylase (noradrenergic fibers), and for vesicular acetylcholine transporter (cholinergic fibers). In mouse joint area, an increase in the ratio of cholinergic to catecholaminergic nerve fibers appeared at day 35 after immunization. Most of the nerve fibers were located in joint-adjacent skin or muscle tissue, and only very few were detected in synovial tissue or near erosions. In human tissue sections, we were able to show cholinergic fibers in the synovium of four OA patients but in none of the RA patients. Co-culture of sympathetic ganglia and osteoclast progenitors from healthy mice showed more catecholaminergic-to-cholinergic transition when compared to experiments with osteoclast progenitors from arthritic mice. In mice and men, catecholaminergic-to-cholinergic transition is possible in less synovial inflamed tissue but not in highly inflamed arthritic tissue.