G. Sisask et al., THE DEVELOPMENT OF AUTONOMIC INNERVATION IN BONE AND JOINTS OF THE RAT, Journal of the autonomic nervous system, 59(1-2), 1996, pp. 27-33
The development of autonomic nerves in the hindlimb skeleton, was stud
ied in rats from gestational day (G) 15 to postnatal day (P) 24 by imm
unoreactivity to neuropeptide Y (NPY) and vasoactive intestinal peptid
e (VIP). Control labelling with antisera to neurofilaments, protein ge
ne-product 9.5 (PGP 9.5), and nerve terminals, synaptophysin (SYN), sh
owed nerve fibres at G15 and nerve terminals at G19 in the perichondri
al tissue. From P4, nerve fibres and terminals were observed within th
e bone organ. Noradrenergic sympathetic nerves, containing NPY, were f
irst discerned at birth, G21, in the perichondrial tissue and within t
he bone organ at P4. Autonomic cholinergic nerve fibres, indicated by
immunoreactivity to VIP, exhibited a similar temporal and regional occ
urrence. The diaphyseal parts were first supplied with autonomic nerve
s at P4. The nerve fibres extended into the metaphyses at P6-8 and fin
ally into the epiphyses at P10, concomitant with the first signs of mi
neralization. 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 that the growth of nerves parallels the minera
lisation process. Previous studies have demonstrated that NPY potently
inhibits parathyroid hormone (PTH) induced effects on osteoblastic bo
ne 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.