Collagen-induced arthritis impairs osteoclastogenesis and reactivity to sympathetic neurotransmitter stimuli in bone marrow-derived macrophages from DA rats

Abstract

Osteoclasts (OC) are key players in bone destruction in rheumatoid arthritis (RA). Recent work showed that catecholaminergic nerve fibers are reduced in RA synovial tissue. Studies on sweat gland innervation revealed that catecholaminergic fibers are capable of phenotypic transition to cholinergic nerves. The sympathetic neurotransmitters norepinephrine (NE) and acetylcholine (ACh) affect osteoclastogenesis oppositely and that is why we wanted to study osteoclastogenesis at different phases of collagen-induced arthritis (CIA) in an altered neurotransmitter microenvironment. The influence of NE and ACh on differentiation and activity of bone marrow macrophage (BMM)-derived osteoclasts from arthritic and control animals were compared at various time-points after arthritis induction. The expression profile for adrenergic and ACh receptors was analyzed on mRNA level. The number of OCs was tendentially lower in arthritic animals. Stimulation with ACh yielded significantly more OCs in controls. NE decreased osteoclastogenesis via β-adrenoceptors and enhanced via α-adrenoceptor stimulation. Cells from arthritic animals were less affected. In form of a trend, osteoclasts from arthritic animals showed decreased activity in cathepsin K activity and in a pit formation assay. The receptor gene expression profile changed in the time course of arthritis. After 20 days past immunization, muscarinic ACh receptors M3 and M5 were significantly upregulated whereas after 40 days adrenoceptors α1D and α2B were significantly downregulated. We conclude that CIA suppresses OC differentiation and activity as well as reactivity to neurotransmitter stimulation but the underlying processes remain to be demonstrated.