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Abstract
The development of autonomic nerves in the hindlimb skeleton, was studied in rats
from gestational day (G) 15 to postnatal day (P) 24 by immunoreactivity to neuropeptide
Y (NPY) and vasoactive intestinal peptide (VIP). Control labelling with antisera to
neurofilaments, protein gene-product 9.5 (PGP 9.5), and nerve terminals, synaptophysin
(SYN), showed nerve fibres at G15 and nerve terminals at G19 in the perichondrial
tissue. From P4, nerve fibres and terminals were observed within the bone organ. Noradrenergic
sympathetic nerves, containing NPY, were first discerned at birth, G21, in the perichondrial
tissue and within the bone organ at P4. Autonomic cholinergic nerve fibres, indicated
by immunoreactivity to VIP, exhibited a similar temporal and regional occurrence.
The diaphyseal parts were first supplied with autonomic nerves at P4. The nerve fibres
extended into the metaphyses at P6-8 and finally into the epiphyses at P10, concomitant
with the first signs of mineralization. Vascular as well as non-vascular nerve fibres
were seen. The study shows that developing bone organ is supplied with autonomic nerves
from birth, and the the growth of nerves parallels the mineralisation process. Previous
studies have demonstrated that NPY potently inhibits parathyroid hormone (PTH) induced
effects on osteoblastic bone cells and that VIP is a strong inductor of bone resorption.
NPY and VIP also exert vasoregulatory effects. The combined findings suggest an autonomic
influence on bone development.