Expression of VEGF and pleiotrophin in deer antler

Abstract

Deer antlers represent a unique model of mammalian regeneration in that they cast and fully regenerate every year. The deer antler thus provides a fascinating model of both rapid angiogenesis and chondrogenesis and the opportunity to investigate unique growth regulatory processes. One such phenomenon is the presence of vascularized cartilage in the growing antler tip-unlike other cartilage, which is typically avascular. The mechanisms by which blood vessels grow in the cartilage as well as the factors that drive antler extension at approximately 1 cm a day have been hitherto largely unknown. The aim of this study was to determine the expression of VEGF and pleiotrophin within the growing antler tip. We isolated cervine VEGF121 and VEGF165 from deer antler and found that mRNA is produced for VEGF in the precartilage and cartilage regions. By in situ hybridization, we examined whether the VEGF receptors Flt-1 and KDR are present in deer antler and found only KDR mRNA within the endothelial cells of the precartilage region. This finding is compatible with VEGF having an angiogenic effect within antler. Pleiotrophin mRNA was found in the vascular smooth muscle cells of the dermis, thus supporting a possible role in vascular growth. High levels of pleiotrophin mRNA were also detected in the precartilage region with possible implications for both angiogenesis and chondrogenesis. This is the first report of cervine angiogenic growth factors within the growing antler tip. Anat Rec Part A, 288A: 1281-1293, 2006. 2006 Key words: angiogenesis; cartilage; chondrogenesis; endothelial Systems where growth occurs at an astonishing rate such as the placenta, embryo, and deer antler can give important insights into the mechanisms involved in angiogenesis. Deer antlers are unique mammalian appendages in that they have an annual cycle of regeneration. During regeneration, the cartilage, skin, nerves, and blood vessels of the antler must grow at a rapid rate. This full regrowth occurs under conditions of low testosterone and high plasma IGF-1 during spring (Li et al., 2003). Antler grows at varying rates in different species, with growth rates reaching 12.5 mm/day in sika deer (Gao and Li, 1988), 27.5 mm/day in moose (Goss, 1970), and approximately 10 mm/day in red deer (Fennessy et al., 1991). Antler growth is driven from the tip, which consists of dermis, mesenchyme, precartilage, and the cartilage that transforms to bone and that then progressively calcifies within the antler (Fig. 1). Antlerogenic stem cells have been found to be concentrated in the reserve mesenchyme underlying the dermis (Li et al., 2002(Li et al., , 2005a. Cells from the reserve mesenchyme divide and differentiate, thus contributing chondroblasts to the precartilage region, where progressive maturation occurs. The cartilage zone contains columns of chondrocytes and large parallel vascular channels, which give a red appearance. In the region shown as the remodeling zone (Fig. 1) THE ANATOMICAL RECORD PART A 288A: 1281-1293 (2006) expand at a rapi...

An activity-maintaining sequential protein extraction method for bioactive assay and proteome analysis of velvet antlers

“…These results are consistent with the reports that precartilage region in antler tip is characterized by impressively proliferation of the vascular associated cells [4], and is likely to contain factors that specifically regulate the growth of blood vessels. Additionally, pleiotrophin [5], an angiogenic factor, was found in this study, which might contribute to the promoting effect on proliferation of HUVEC.…”

“…Therefore, antlers are considered as valuable models for studying the signaling pathways which modulates the development of these tissues. Recent evidence suggests that antler regeneration is a stem cell-based process, and some growth factors, such as VEGF, EGF, FGF and NGF, have been proved to be involved in the exceptional growth [4][5][6][7], in which some undiscovered modulating factors with low abundance or short-half-life in development of normal tissues may be over-expressed and more likely be found. Thus, investigation on the activities of proteins extracted from velvet antlers might lead to the founding of new active factors which play roles in the development of tissues mentioned above.…”

Antler velvet is thicker in adult than in yearling pampas deer (Ozotoceros bezoarticus): a histological study

“…Interestingly, Clark et al [4] reported presence of pleiotropin mRNA both in the antler tip and in its velvet dermis. Pleiotropin is considered a strong angiogenic factor [9] and might explain the abundant dermal irrigation we are reporting.…”

The effect of deer antler growth factor on the viability and proliferation of primary human alveolar osteoblast cells in vitro

“…To investigate the cascade of events leading to rapid growth and osteogenic activity, current research has focused on identifying and characterizing trophic factors present in the regeneration phase of this organ. Besides, the effects of hormones, growth factors such as insulin-like growth factor, epidermal growth factor, vascular endothelial growth factor, nerve growth factor, as well as bone morphogenetic proteins, have been shown to play important roles in regeneration processes of deer antler [1,4,10,15,17].…”