THE DEVELOPMENT OF AUTONOMIC INNERVATION IN BONE AND JOINTS OF THE RAT

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.