Demonstration of Direct Neurite–Osteoclastic Cell Communication In Vitro via the Adrenergic Receptor

Abstract

There is currently great interest in the bone metabolism induced by the sympathetic nerve system. Recently, direct neurite–osteoblastic cell communication was demonstrated using an in vitro co-culture model comprising neurite-sprouting murine superior cervical ganglia and MC3T3-E1 osteoblast-like cells. In the present study, we examined whether the direct nerve–osteoclastic cell communication was present in an in vitro co-culture model comprising cultured murine superior cervical ganglia and mouse osteoclast-like cells. RAW264.7 cells treated with receptor activator of NF-κB ligand were used as osteoclast-like cells. We found that the addition of scorpion venom (SV) elicited neurite activation via intracellular Ca²⁺ mobilization and, after a lag period, osteoclastic Ca²⁺ mobilization in the co-culture. SV did not have any direct effect on the osteoclastic cells in the absence of the neurites. The addition of an α₁-adrenergic receptor (AR) antagonist, prazosin, concentration-dependently prevented the osteoclastic activation that resulted as a consequence of neural activation by SV. We also found that α₁-adrenergic receptor agonists evoked transient Ca²⁺ mobilization and gene expression of interleukin-6 in osteoclastic cells. These results demonstrate that osteoclastic activation occurs via α₁-AR in osteoclastic cells as a direct response to neuronal activation.