Calcitonin gene‐related peptide (CGRP)‐containing nerve fibers in bone tissue and their involvement in bone remodeling

Abstract

Bone remodeling is a process of bone renewal accomplished by osteoclastic bone resorption and osteoblastic bone formation. These two activities are regulated by systemic hormones and by local cytokines and growth factors. Moreover, the nervous system and certain neuropeptides seem to be involved in regulation of bone remodeling. In this paper, we focus on the distribution of CGRP-containing nerve fibers and their dynamics, and discuss the role of these fibers as a possible mechanism for nervous system involvement in regulation of bone remodeling. CGRP-immunoreactive nerve fibers are widely distributed in bone tissue, such as periosteum and bone marrow, and show apparent regional distribution with different densities. They are often associated with blood vessels and show a beaded appearance. The wide distribution of CGRP-immunoreactive nerve fibers in bone tissue and the changes in distribution during bone development and regeneration suggest the involvement of these fibers in bone remodeling. The effect of CGRP on bone remodeling could partly be through its action on blood vessels, thereby regulating local blood flow. Moreover, in vitro biochemical data and the localization of CGRP-immunoreactive nerve fibers in the vicinity of bone cells suggest that they are directly involved in local regulation of bone remodeling by elevating the concentration of CGRP in the microenvironment around bone cells, especially during bone growth or repair.

Calcitonin gene-related peptide stimulates BMP-2 expression and the differentiation of human osteoblast-like cells in vitro

“…A number of studies have confirmed that activation of osteoblastic CGRP receptors results in enhanced www.chinaphar.com Tian G et al Acta Pharmacologica Sinica npg osteoblast proliferation [8] , and CGRP also increases the synthesis of growth factors and cytokines [including IGF-1 (insulinlike growth factor)], collagen synthesis and bone formation in vivo [1] . However, the signaling pathways by which CGRP exerts its osteogenic effects in osteoblasts are unclear.…”

“…E-mail tanyhoms@yahoo.cn Received 2012-10-30 Accepted 2013-03-25 in nerve fibers during bone development and repair [1,2] .…”

“…In response to fracture or other trauma, peripheral peptidergic neurons can influence osteoclast formation through the production of several neuropeptides. Calcitonin gene-related peptide (CGRP), a 37-residue peptide generated in specific neurons by alternative splicing of the calcitonin gene, is an important neuropeptide expressed in nerve fibers during bone development and repair [1,2] .…”

“…While CGRP promotes the production of BMP-2 in pulp cells [23,24] , BMP-2 is also associated with the spatial and temporal regeneration of CGRP-positive nerve fibers in ectopic bone formation [25] . Neuropeptides and receptors such as CGRP play important roles in the regulation of bone remodeling [1] , and CGRP induces BMP-2 expression in bone tissues [23,26] . We hypothesized that BMP-2 expression is involved in CGRPinduced osteogenesis.…”

“…In response to fracture or other trauma, peripheral peptidergic neurons can influence osteoclast formation through the production of several neuropeptides. Calcitonin gene-related peptide (CGRP), a 37-residue peptide generated in specific neurons by alternative splicing of the calcitonin gene, is an important neuropeptide expressed * To whom correspondence should be addressed.E-mail tanyhoms@yahoo.cn Received 2012-10-30 Accepted 2013-03-25 in nerve fibers during bone development and repair [1,2] .Numerous in vivo studies have suggested that CGRP is associated with bone development, metabolism and repair. In vitro studies have demonstrated that CGRP stimulates osteoblast proliferation, differentiation and maturation in both osteoblast cell lines and bone marrow mesenchyme stromal cells.…”