Development of sensory innervation in rat tibia: co‐localization of CGRP and substance P with growth‐associated protein 43 (GAP‐43)

Abstract

The development of sensory innervation in long bones was investigated in rat tibia in fetuses on gestational days (GD) 16 -21 and in neonates and juvenile individuals on postnatal days (PD) 1-28. A double immunostaining method was applied to study the co-localization of the neuronal growth marker growth-associated protein 43 (GAP-43) and the pan-neuronal marker protein gene product 9.5 (PGP 9.5) as well as that of two sensory fibre-associated neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP). The earliest, not yet chemically coded, nerve fibres were observed on GD17 in the perichondrium of the proximal epiphysis. Further development of the innervation was characterized by the successive appearance of nerve fibres in the perichondrium/periosteum of the shaft (GD19), the bone marrow cavity and intercondylar eminence (GD21), the metaphyses (PD1), the cartilage canals penetrating into the epiphyses (PD7), and finally in the secondary ossification centres (PD10) and epiphyseal bone marrow (PD14). Maturation of the fibres, manifested by their immunoreactivity for CGRP and SP, was visible on GD21 in the epiphyseal perichondrium, the periosteum of the shaft and the bone marrow, on PD1 in the intercondylar eminence and the metaphyses, on PD7 in the cartilage canals, on PD10 in the secondary ossification centres and on PD14 in the epiphyseal bone marrow. The temporal and topographic pattern of nerve fibre appearance corresponds with the development of regions characterized by active mineralization and bone remodelling, suggesting a possible involvement of the sensory innervation in these processes.

Activation of ERK1/2 and PI3K/Akt by IGF-1 on GAP-43 Expression in DRG Neurons with Excitotoxicity Induced by Glutamate In Vitro

“…GAP-43 is a presynaptic protein implicated in axonal growth, neuronal differentiation, plasticity, and regeneration (Chakravarthy et al 2008). GAP-43 is an axonal regeneration marker (Murata et al 2006;Aoki et al 2007;Kimura et al 2007;Anand et al 2008) and a neuronal growth marker (Gajda et al 2005;Mechsner et al 2007;Zinck et al 2007). It has been reported that local h Quantitative analysis of the ratio of apoptotic cells at different experimental conditions.…”

Estrogen receptor-α expression in neuronal cells affects bone mass

“…It is now recognized that the regulation of bone involves other systems within the organism, including the CNS. It has been known for long time that bone is an innervated tissue containing both efferent and afferent fibers in bone marrow and the periosteum (1). However, the first clear evidence that central signaling affects bone mass was the finding that leptin-deficient mice, despite their hypogonadism, had high bone mass, and that this phenotype was reversed by intracerebroventricular injections of leptin (2).…”

Bone and Cartilage – its Structure and Physical Properties

“…Gajda et al [128] investigated the development of sensory innervation in long bones, see Figure 1.18. Their model was rat tibia in fetuses and in juvenile individuals on postnatal days.…”