Oncostatin M in the development of the nervous system

Abstract

Oncostatin M (OSM) is a member of the interleukin-6 family of cytokines. Of these cytokines, OSM is closely related structually, genetically and functionally to leukemia inhibitory factor. However, OSM-specific biological activities have been reported in hematopoiesis and liver development. Recently, we have demonstrated OSM-specific activities in the nervous systems. In the adult central nervous system (CNS), OSM receptor (OSMR) beta was observed in meningeal cells of pia mater, epithelial cells of the choroid plexus and olfactory astrocyte-like glia surrounding the glomeruli of the olfactory bulb. In the CNS of neonatal mice, OSMRbeta was also expressed in the ventral subnucleus of the hypoglossal nucleus, but disappeared at post-natal day (P) 14. In contrast with the CNS, OSMRbeta was strongly expressed in small-sized non-peptidergic neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG). Interestingly, all OSMRbeta-positive neurons in these ganglia also expressed both TRPV1 (a vanilloid receptor) and P2X3 (a purinergic receptor). In OSM-deficient mice, TRPV1/P2X3/OSMRbeta triple-positive neurons were significantly decreased. Consistent with such histological findings, OSM-deficient mice exhibited a reduction in responses to various stimuli, including mechanical and thermal stimuli. These findings suggest an important role for OSM in the development of a subset of nociceptive neurons.