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Neuronal regulation of bone metabolism and anabolism: Calcitonin gene‐related peptide‐, substance P‐, and tyrosine hydroxylase‐containing nerves and the bone
Author(s) -
Imai Shinji,
Matsusue Yoshitaka
Publication year - 2002
Publication title -
microscopy research and technique
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 118
eISSN - 1097-0029
pISSN - 1059-910X
DOI - 10.1002/jemt.10119
Subject(s) - medicine , endocrinology , bone remodeling , anabolism , tyrosine hydroxylase , neuropeptide , calcitonin gene related peptide , bone cell , calcitonin , biology , substance p , chemistry , dopamine , receptor
Bone alters its metabolic and anabolic activities in response to the variety of systemic and local factors such as hormones and growth factors. Classical observations describing abundance of the nerves fibers in bone also predict a paradigm that the nervous system influences bone metabolism and anabolism. Identification of the nerve‐derived signaling molecules, capable of modulating cellular activities of the bone cells, facilitates a novel approach to study the biology of skeletal innervation. Many of the signaling molecules that may act as efferent agents on the bone cells fall into the category of neuropeptides. The present article reviews current understanding of the skeletal innervation and their proposed physiological effects on bone metabolism, with a special interest to calcitonin gene‐related peptide (CGRP)‐containing nerves fibers. CGRP is abundantly distributed in bone via sensory nerves, especially in the epiphyseal trabecular bones. Its in vitro actions to the cultured osteoblasts and osteoclasts, together with its in vivo localization, strongly support the paradigm that the nervous system influences bone metabolism. In addition, CGRP is recently shown to be expressed endogenously by the osteoblasts. Transgenic mice with osteoblasts overexpressing CGRP are characterized by increased bone formation rate and enhanced bone volume, suggesting that CGRP indeed acts on bone metabolism not only via nervous route but also via autocrine loop. The current article also reviews the distribution of nerve fibers containing substance P (SP), another sensory nerve‐specific neuropeptide, and tyrosine hydroxylase (TH), the rate‐limiting enzyme of catecholamine. The distinct effects of SP and catecholamines on the bone cells together with their in vivo influences manifested by experimental denervation studies suggest that the sensory and sympathetic nerves play important roles in bone metabolism. Microsc. Res. Tech. 58:61–69, 2002. © 2002 Wiley‐Liss, Inc.