Evidence for a dense and intimate innervation of the bone tissue, including glutamate-containing fibers

The recent demonstration in bone cells of receptors for glutamate (Glu), a major neuromediator, suggests that Glu may also act as a signaling molecule in bone and regulate bone cell metabolism. Although bone is known to be in nervated, the distribution and characteristics of nerve fibers in this tiss ue have not been well documented. We have studied the anatomical distributi on of nerve fibers and the presence of glutamate-immunoreaetive ones in sec tions of long bones from neonatal, 15-, and 25-day-old rats, using immunocy tochemistry with antibodies directed against several neuronal markers and G lu, We showed by electron microscopy that bone is rich in nerve-like proces ses running along vessels adjacent to bone trabeculae, in the vicinity of h ematopoietic cells and bone cells, Immunocytochemical studies at the tissue and cellular level confirmed the presence of a dense network of thin nerve processes immunolabeled for neurofilament 200, tyrosine hydroxylase, and m icrotubule associated protein-2, three markers of nerve fibers. Some of the se nerve processes showed local dilatations in contact with medullary cells and bone cells that were immunolabeled for synaptophysin, a nerve terminal marker. Glu was largely expressed in these thin nerve processes in proximi ty to bone cells. These findings show evidence for a dense and intimate net work of nerve processes in bone, some of which were containing Glu, suggest ing glutamatergic innervation in bone. (C) 1999 by Elsevier Science Inc. Al l rights reserved.