Temporal and Spatial CGRP Innervation in Recombinant Human Bone Morphogenetic Protein Induced Spinal Fusion in Rabbits

Abstract

The observed spatial and temporal regeneration of CGRP-positive nerve fibers in ectopic bone formation suggested CGRP innervation is associated with ectopic osteogenesis.

Involvement of Calcitonin Gene-Related Peptide Innervation in the Promoting Effect of Low-Intensity Pulsed Ultrasound on Spinal Fusion Without Decortication

“…11 High density of CGRP-positive nerve fibers present in the fibrous tissue where the cells intend to differentiate into chondrocytes as well as at the interface between two materials with different mechanical properties. These observations provided an anatomic basis for supporting the hypothesis that CGRP-positive nerve fibers sensed mechanical stimulation and transferred these signals afferently, followed by the release of CGRP from the dorsal horn of spinal cord, 19 transferring efferently to participate in regulation of osteogenesis.…”

“…11 Twelve serial sections from each side were selected to stain with hematoxylin and eosin (H&E) (3 sections), safranin O/fast green (3 sections), and perform immunofluorescent staining (6 sections).…”

“…Briefly, the surgical procedure was carried out using our established protocol. 2,11 The rabbits were anesthetized using intravenous ketamine (10 mg/kg) together with xylazine (3 mg/kg). Through a midline longitudinal posterior insertion, the transverse processes of L5-L6 and adjacent lateral surface of facet joints were exposed subperiosteally with a fine periosteal elevator, and the interface and intertransverse processes tissues were cleaned down to the intertransverse process.…”

“…11 Briefly, the sections were rinsed in phosphate buffered saline to remove traces of fixative. After incubation in normal bovine serum for 2 hours at room temperature to block nonspecific binding of antibodies; the sections were then incubated with the goat polyclonal CGRP primary antibody (Santa Cruz, CA; diluted 1:50) for 24 hours at 4°C.…”

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

“…Previous studies suggest that BMPs 2, 4, or 6 stimulate CGRP expression in 60% of DRG neurons [22] . 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] .…”