The occurrence of neuropeptides at different stages of DBM-induced heterotopic bone formation.

In developing heterotopic bone in the rat, induced by allogeneic bone matrix, we immunohistochemically detected nerves containing substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and tyrosine hydroxylase (TH). After 10 days they were dicernible amidst differentiating chondroblastoid cells in fibrous tissue around and within the implants. Over the next 3 weeks, the nerves increased in number and gradually attained a shape and distribution resembling normal osseal nerves; varicose fibres frequently occurred in periosteum-like fibrous tissue and bone marrow adjacent to newly formed bone. At 8 weeks, NPY-fibres increased, particularly in the marrow and this abundance of NPY fibres remained at 16 weeks. VIP-immunoreactive fibres were only observed in the surrounding periosteum-like fibrous tissue 4-6 weeks after implantation. These observations, in combination with recent findings of receptors to neuropeptides on bone cells, suggest a neurogenic influence on physiological processes in bone tissue.