ONTOGENY OF SENSORY NERVES IN THE DEVELOPING SKELETON

Background: Previous studies have shown that the neuropeptide calciton in gene-related peptide (CGRP) have an influence on osteoclastic bone resorption and that CC;RP and substance P (SP), both well-known marker s for sensory neurons, behave as growth factors, Materials and Methods : The ontogeny of the sensory nerves in the hindlimb skeleton of the r at was studied from gestational day (GD) 15 to neonatal day (ND) 24 by immunohistochemistry. Neurofilaments and nerve terminals were labelle d with protein gene-product 9.5 (PGP 9.5) and synaptophycin (SYN), res pectively, Results: PGP 9.5 appeared at GD 15 and SYN at GD 19, both i n 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 th e bone organ. Sensory nerves, indicated by CGRP and SP, were first dis cerned at GD 18-19 in the periosteal tissue of the diaphyseal and meta physeal regions and in the bone organ at ND 4, Approximately at ND 6, vascular as well as non-vascular nerves extended into the metaphyses a nd at ND 8 into the epiphyses, concomitant with the first signs of min eralization. Conclusions: The study shows that a functional sensory ne rve supply of the developing bone organ occurs immediatly prior to par tus, apparently parallel with an increasing mineralization. The combin ed findings may indicate a sensory influence on developmental processe s in the skeleton. (C) 1995 Wiley-Liss, Inc.