Rapid neural growth: Calcitonin gene-related peptide and substance P-containing nerves attain exceptional growth rates in regenerating deer antler

Gray, Colin; Hukkanen, Mika; Konttinen, Yrjö T.; Terenghi, Giorgio; Arnett, TR; Jones, Siana; Burnstock, Geoffrey; Polak, Julia M.

doi:10.1016/0306-4522(92)90218-q

Cited by 36 publications

(33 citation statements)

References 39 publications

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“…These authors found no fibres containing PGP 9·5, NF, substance P or CGRP in cartilaginous and ossified tissues. Although it has been observed that antler nerves tend to grow out alongside the major arteries in the velvet (Suttie & Fennessy 1985), free nerve fibres are apparently present in the deeper connective tissues as well (Gray et al 1992). The moderate to minor amounts of NT-3 expression observed in the reserve mesenchymal, pre-cartilaginous and cartilaginous layers of the growing antler tip may represent pockets of cells able to produce and deliver NT-3 to sensory nerves in the adjacent tissues by a paracrine mechanism.…”

Section: Discussionmentioning

confidence: 96%

“…The dermal layer has been shown to be the most densely innervated, notably in the deeper connective tissues. Gray et al (1992) found fibres immunoreactive to substance P, CGRP and neurofilament triplet protein (NF, a neural cytoskeletal protein) antisera in these tissues and in the sub-epidermis. Immunoreactivity to protein gene product 9·5 (PGP 9·5, a neural cytoplasmic protein) was also observed near the epidermis (Gray et al 1992).…”

Section: Discussionmentioning

confidence: 96%

“…Gray et al (1992) found fibres immunoreactive to substance P, CGRP and neurofilament triplet protein (NF, a neural cytoskeletal protein) antisera in these tissues and in the sub-epidermis. Immunoreactivity to protein gene product 9·5 (PGP 9·5, a neural cytoplasmic protein) was also observed near the epidermis (Gray et al 1992). These authors found no fibres containing PGP 9·5, NF, substance P or CGRP in cartilaginous and ossified tissues.…”

Section: Discussionmentioning

confidence: 96%

“…Antlers are normally supplied only with sensory nerves (Wislocki & Singer 1946) and lack sympathetic innervation (Wika 1980, Rayner & Ewen 1981, Gray et al 1992. Both myelinated and unmyelinated fibres have been observed in the epidermis and in the vascularised dermal tissue (Vacek 1955).…”

Section: Introductionmentioning

confidence: 99%

“…Innervation occurs by the regeneration of pedicle nerves (Waldo et al 1949). Unlike other cellular components of the antler which develop in situ, blood vessels and nerves invade the forming tissue and are able to grow at the same rapid rate as the antler (Gray et al 1992).…”

Section: Introductionmentioning

confidence: 99%

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Expression of neurotrophin-3 in the growing velvet antler of the red deer Cervus elaphus

Garcia¹,

Sadighi²,

Francis³

et al. 1997

Journal of Molecular Endocrinology

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Antlers are organs of bone which regenerate each year from the heads of male deer. In addition to bone, support tissues such as nerves also regenerate. Nerves must grow at up to 1 cm/day. The control of this rapid growth of nerves is unknown. We examined the relative expression of neurotrophin-3 (NT-3) mRNA in the different tissues of the growing antler tip and along the epidermal/ dermal layer of the antler shaft of the red deer Cervus elaphus, using semi-quantitative reverse transcription-polymerase chain reaction. Expression in the tip was found to be highest in the epidermal/dermal layer and lowest in the cartilaginous layer in all developmental stages examined. These data correlate well with the density and pattern of innervation of these tissues. Along the epidermal/dermal layer of the antler shaft, expression was highest in the segments subjacent to the tip and lowest near the base, arguing for differences in the temporal expression of NT-3 in these segments. The expression of NT-3 in cells isolated from the different layers of 60-day antlers did not mirror that observed when whole tissues were used and may suggest regional specificity of NT-3 expression within antler tissues.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Expression of neurotrophin-3 in the growing velvet antler of the red deer Cervus elaphus

Garcia¹,

Sadighi²,

Francis³

et al. 1997

Journal of Molecular Endocrinology

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Deer antler regeneration: A stem cell‐based epimorphic process

Li¹

2012

Birth Defects Research Pt C

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Full regeneration of deer antlers, a bona fide epimorphic process in mammals, is in defiance of the general rule of nature. Revealing the mechanism underlying this unique exception would place us in a better position to promote organ regeneration in humans. Antler regeneration takes place in yearly cycles from its pedicle, a permanent protuberance on the frontal bone. Both growing antlers and pedicles consist of internal (cartilage and bone) and external components (skin, blood vessels, and nerves). Recent studies have demonstrated that the regeneration of both internal and external components relies on the presence of pedicle periosteum (PP). PP cells express key embryonic stem cell markers (Oct4, Nanog, and SOX2) and are multipotent, so are termed antler stem cells. Now it is clear that proliferation and differentiation of PP cells directly forms internal antler components; however, how PP initiates and maintains the regeneration of external antler components is thus far not known. Based on the direct as well as indirect evidence that is presented in this review, I put forward the following hypothesis to address this issue. The full regenerative ability of external antler tissue components is achieved through PP-derived chemical induction and PP-derived mechanical stimulation: the former triggers the regeneration of these external components, whereas the latter drives their rapid elongation. Eventual identification of the putative PP-derived chemical factors would open up a new avenue for devising effective therapies for lesions involving each of these tissue components, be they traumatic, degenerative, or linked to developmental (genetic) anomalies.

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The neuropeptide VIP regulates the expression of osteoclastogenic factors in osteoblasts

Persson¹,

Lerner²

2011

J. Cell. Biochem.

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Osteoclast formation is controlled by stromal cells/osteoblasts expressing macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL), crucial for osteoclast progenitor cell proliferation, survival and differentiation, and osteoprotegerin (OPG) that inhibits the interaction between RANKL and its receptor RANK. Recent data have strongly indicated that the nervous system plays an important role in bone biology. In the present study, the effects of the neuropeptide vasoactive intestinal peptide (VIP), present in peptidergic skeletal nerve fibers, on the expression of RANKL, OPG, and M-CSF in osteoblasts and stromal cells have been investigated. VIP and pituitary adenylate cyclase-activating polypeptide 38 (PACAP-38), but not secretin, stimulated rankl mRNA expression in mouse calvarial osteoblasts. In contrast, VIP inhibited the mRNA expressions of opg and m-csf, effects shared by PACAP-38, but not by secretin. VIP did not affect rankl, opg, or m-csf mRNA expression in mouse bone marrow stromal cells (BMSCs). The effects by VIP on the mRNA expression of rankl, opg, and m-csf were all potentiated by the cyclic AMP phosphodiesterase inhibitor rolipram. In addition, VIP robustly enhanced the phosphorylation of ERK and the stimulatory effect by VIP on rankl mRNA was inhibited by the MEK1/2 inhibitor PD98059. These observations demonstrate that activation of VPAC(2) receptors in osteoblasts enhances the RANKL/OPG ratio by mechanisms mediated by cyclic AMP and ERK pathways suggesting an important role for VIP in bone remodeling.

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Rapid neural growth: Calcitonin gene-related peptide and substance P-containing nerves attain exceptional growth rates in regenerating deer antler

Cited by 36 publications

References 39 publications

Expression of neurotrophin-3 in the growing velvet antler of the red deer Cervus elaphus

Expression of neurotrophin-3 in the growing velvet antler of the red deer Cervus elaphus

Deer antler regeneration: A stem cell‐based epimorphic process

The neuropeptide VIP regulates the expression of osteoclastogenic factors in osteoblasts

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