Bone Abstracts

Osteoclast (OC)-mediated bone destruction is a key feature of rheumatoid arthritis (RA). In RA synovial tissue a reduced density of catecholaminergic nerve fibres has been observed. Studies on sweat gland innervation proved that catecholaminergic fibres have the ability to undergo a phenotypic transition to cholinergic nerves. The sympathetic neurotransmitters norepinephrine (NE), acetylcholine (ACh), and vasoactive intestinal peptide (VIP) affect osteoclastogenesis oppositely and in this context we wanted to study osteoclastogenesis at different phases of collagen-induced arthritis (CIA) in DA rats.

The influence of NE, ACh, and VIP on differentiation and activity of bone marrow macrophage-derived osteoclasts from CIA and control animals are compared at various time-points post immunization (pI). The expression profile for NE, ACh, and VIP neurotransmitter receptors is analyzed on mRNA and protein level.

OC numbers were tendentially lower in arthritic animals. ACh stimulation markedly elevated OC formation in controls (15 and 40 days pI). NE decreased osteoclastogenesis via β-adrenoceptors and enhanced via α-adrenoceptor stimulation. VIP time-point dependently inhibited (10 and 15 days pI) or stimulated (20 and 40 days pI) osteoclastogenesis. Cells from arthritic animals were less affected. By trend, osteoclasts from arthritic animals showed decreased activity in a cathepsin K activity and in a matrix degradation assay.

Receptor gene expression changed in the time course of arthritis. 20 days past immunization muscarinic ACh receptors M3 and M5 were significantly upregulated, whereas VIP receptor PACR1 was significantly downregulated. After 40 days adrenoceptors α1D and α2B were significantly downregulated. So far, on protein level we analyzed β2 adrenoceptor expression and localization and could not find any CIA-induced changes.

We conclude that CIA suppresses OC differentiation and activity as well as reactivity to neurotransmitter stimulation but the underlying processes remain unknown as yet. NE, ACh, and VIP receptor gene expression was affected time-point dependently but the physiological impact needs further investigation.