Vasoactive intestinal peptide regulates osteoclast activity via specific binding sites on both osteoclasts and osteoblasts

Clinical and experimental observations, together with immunohistochemical f indings, suggest that neuro-osteogenic interactions may occur in the skelet on. In this study, we have examined the effect of vasoactive intestinal pep tide (VIP), one of the neuropeptides present in bone, on the activity of th e bone-resorbing osteoclast, Effects on bone resorption were assessed by co unting the number of pits formed by rat osteoclasts incubated on devitalize d slices of bovine cortical bone. Under conditions with an initially sparse density of stromal cells/osteoblasts, VIP caused a rapid cytoplasmic contr action and decreased motility of osteoclasts. This was coupled with a decre ase in the number of resorption lacunae and a decrease in the total area re sorbed by the osteoclasts in 48-h cultures. Time-course experiments reveale d that the inhibitory effects on contraction and motility were transient an d that the cells gradually regained their activity, such that, when culture time was prolonged to 120 h, a stimulatory effect by VIP on bone resorptio n was observed. When osteoclasts were incubated on bone slices, in the pres ence of an initially large number of stromal cells/osteoblasts, VIP treatme nt increased the number of resorption pits and total bone area resorbed in 48-h cultures. Using atomic force microscopy, we provide direct evidence th at both osteoclasts and stromal cells/osteoblasts bind VIP. Also, VIP was s hown to cause a rapid rise of intracellular calcium in osteoclasts and in a proportion (20%) of stromal cells/osteoblasts, Taken together, these data suggest that differentiated osteoclasts are equipped with receptors for VIP that are linked to a transient inhibition of osteoclast activity and, in a ddition, that stromal cells/osteoblasts have VIP receptors coupled to a del ayed stimulation of osteoclastic resorption, (C) 2000 by Elsevier Science I nc. All rights reserved.