Ontogeny of sensory nerves in the developing skeleton.

Abstract

AbstractBackground: Previous studies have shown that the neuropeptide calcitonin gene‐related peptide (CGRP) have an influence on osteoclastic bone resorption and that CGRP and substance P (SP), both wellknown markers for sensory neurons, behave as growth factors.Materials and Methods: The ontogeny of the sensory nerves in the hindlimb skeleton of the rat was studied from gestational day (GD) 15 to neonatal day (ND) 24 by immunohistochemistry. Neurofilaments and nerve terminals were labelled with protein gene‐product 9.5 (PGP 9.5) and synaptophycin (SYN) respectively.Results: PGP 9.5 appeared at GD 15 and SYN at GD 19, both in the perichondrial tissue of the long bones. One week later, at ND 4 nerve fibre, immunoreactive to PGP 9.5 and SYN were observed within the bone organ. Sensory nerves, indicated by CGRP and SP, were first discerned at GD 18–19 in the periosteal tissue of the diaphyseal and metaphseal regions and in the bone organ at ND 4. Approximately at ND 6, vascular as well as non‐vascular nerves extended into the metaphyses and at ND 8 into the epiphyses, concomitant with the first signs of mineralization.Conclusions: The study shows that a functional sensory nerve supply of the developing bone organ occurs immediatly prior to partus, apparently parallel with an increasing mineralization. The combined findings may indicate a sensory influence on developmental processes in the skeleton. © 1995 Wiley‐Liss, Inc.