Background/Purpose: 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 (see innervation of sweat gland and periosteum). This can be important because anti-inflammatory effects of acetylcholine have been described which is mainly mediated by the α7nicotinic acetylcholine receptor. We asked whether this transition could also occur in the joint during collagen-induced arthritis (CIA) in mice or during rheumatoid arthritis (RA) and osteoarthritis (OA) in humans.

Methods: Arthritic limbs from 30 immunized C57Bl/6J mice were collected at distinct time points covering all stages of the disease. Sections of mouse limbs and synovial tissue samples obtained from 30 OA and 12 RA patients were stained for tyrosine hydroxylase (TH, noradrenergic fibers), and for vesicular acetylcholine transporter (VAChT, cholinergic fibers). For co-culture experiments, sympathetic ganglia were obtained from newborn mice and double-stained for TH and VAChT after a co-culture period of two to three days with osteoclast progenitors attained from the femoral and tibial bonemarrow as well as lymphocytes obtained from the draining lymph nodes and fibroblast-like cells isolated from the paws of adult mice.

Results: 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 synovial tissue of four OA patients but in none of the RA patients. Co-cultures of sympathetic ganglia and osteoclast progenitors as well as lymphocytes and fibroblast-like cells obtained from healthy mice showed more catecholaminergic-to-cholinergic transition when compared to experiments with the respective cells from arthritic mice.

Conclusion: In men and mice, catecholaminergic-to-cholinergic transition is possible in less inflamed tissue of the joint but not in highly inflamed arthritic tissue.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/osteoclast-progenitors-fibroblast-like-cells-and-draining-lymph-node-cells-induce-catecholaminergic-to-cholinergic-transition-of-sympathetic-nerve-fibers-under-healthy-conditions-but-not-in-highly-in/