Identification of axon growth promoters in the secretome of the deer antler velvet.
Every spring, deer cast their old antlers and initiate a regeneration process, which yields a new set of antlers of up to 1m in length. Over the course of three months, branches of the trigeminal nerve, originating from the frontal skull, innervate velvet, a modified skin that covers the regenerating antler. The rate of growth of these axons reaches up to 2cm per day making them the fastest regenerating axons in adult mammals. Here, we aim to identify the factors secreted by velvet that promote such high speed axon growth. Our experiments with cultures of adult rat trigeminal neurons demonstrate that conditioned medium harvested from velvet organotypic cultures has greater axon growth-promoting properties than a medium conditioned by normal skin. The axon growth-promoting effects of velvet act synergistically with the extracellular matrix (ECM) protein laminin, a component of the basal lamina present in the deer antler. Our proteomic analyses identified several axon growth promoters in the velvet-conditioned medium (VCM), including soluble proteins such as nerve growth factor (NGF) and apolipoprotein A-1, as well as matrix extracellular proteins, such as periostin and SPARC. Additional in vitro analyses allowed us to determine that a synergic relationship between periostin and NGF may contribute to neurite growth-promoting effects of velvet secretome. A combinatorial approach using these factors may promote regeneration at high speeds in patients with peripheral neuropathies.
Molecular Neuroprotection Group, Experimental Neurology Unit, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain; Department of Neuroscience, Washington University School of Medicine, Saint Louis, MO, USA.
Wolfgang
W
Pita-Thomas
Proteomics Core, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain.
Gemma
G
Barroso-García
Proteomics Core, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain.
Veronica
V
Moral
The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami School of Medicine, Miami, USA.
Amber R
AR
Hackett
Department of Neuroscience, Washington University School of Medicine, Saint Louis, MO, USA.
Valeria
V
Cavalli
Molecular Neuroprotection Group, Experimental Neurology Unit, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain. Electronic address: mnietodiaz@gmail.com.
Manuel
M
Nieto-Diaz
D000818:Animals; D000999:Antlers / Q000378:metabolism*; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D017077:Culture Media, Conditioned; D003670:Deer / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D009414:Nerve Growth Factors / Q000378:metabolism*; D000071446:Neuronal Outgrowth / Q000502:physiology; D020543:Proteome; D017208:Rats, Wistar; D012668:Trigeminal Ganglion / Q000378:metabolism
D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors; D020543:Proteome
axon regeneration; deer antler; peripheral nervous system; proteomics; secreted proteins