Oncomodulin,
an ~12 kDa Ca(2+)-
binding protein secreted from activated macrophages, has been shown to promote axonal regeneration from retinal ganglion cells (RGCs) following
optic nerve injury. However, to date, the axonal growth-promoting capacity of
oncomodulin in other models of 'regenerative failure' has not been evaluated. We assessed the capability of preconditioning treatment with
oncomodulin to promote sensory axonal regeneration in an in vitro spot model of regenerative failure, and across the dorsal root zone (DREZ) after root
crush injury. Neither the direct exposure of adult rat DRGs to
oncomodulin, nor preconditioning of DRGs by intraganglionic injection of
oncomodulin, stimulated axonal outgrowth in the in vitro
proteoglycan spot gradient assay. However, direct exposure of unconditioned DRGs to both
oncomodulin and db-cAMP in vitro, as well as preconditioning of DRGs with the combined treatment in vivo, resulted in significant, albeit modest, neurite extension across the inhibitory
proteoglycan barrier. We next quantified axon regeneration through the C8 DREZ in adult rats after
oncomodulin and/or db-cAMP preconditioning and
chondroitinase (ChABC) injection into the DREZ immediately following a root
crush injury. Axonal regeneration across the DREZ was not observed in control animals, or after injection of ChABC-alone. Treatment with
oncomodulin- or db-cAMP-alone resulted in extremely sparse regeneration. However, significant, but meager, sensory axon regeneration across the DREZ was observed using the
oncomodulin/ db-
cAMP combination (p<0.001), supporting findings from previous studies suggesting that cAMP is necessary for the growth-promoting effects of
oncomodulin. Although our results support a role for
oncomodulin in macrophage-induced axonal regeneration, the effects of
oncomodulin/db-cAMP on sensory regeneration were extremely limited in comparison to previous studies in the same injury model using
zymosan.