title: Linckosides enhance proliferation and induce morphological changes in human olfactory ensheathing cells.
abstract: Linckosides are members of the steroid glycoside family isolated from the starfish Linckia laevigata. These natural compounds have notable neuritogenic activity and synergistic effects on NGF-induced neuronal differentiation of PC12 cells. Neurogenic factors or molecules that are able to mimic their activities are known to be involved in the survival, proliferation and migration of neurons and glial cells; however how glial cells respond to specific neurogenic molecules such as linckosides has not been investigated. This study aimed to examine the effect of three different linckosides (linckoside A, B and granulatoside A) on the morphological properties, proliferation and migration of human olfactory ensheathing cells (hOECs). The proliferation rate after all the treatments was higher than control as detected by MTS assay. Additionally, hOECs displayed dramatic morphological changes characterized by a higher number of processes after linckoside treatment. Interestingly changes in microtubule organization and expression levels of some early neuronal markers (GAP43 and βIII-tubulin) were also observed. An increase in the phosphorylation of ERK 1/2 after addition of the compounds suggests that this pathway may be involved in the linckoside-mediated effects particularly those related to morphological changes. These results are the first description of the stimulating effects of linckosides on hOECs and raise the potential for this natural compound or its derivatives to be used to regulate and enhance the therapeutic properties of OECs, particularly for cell transplantation therapies.
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia. Electronic address: j.tellovelasquez@griffith.edu.au.
authors.forename: Johana
authors.initials: J
authors.lastname: Tello Velasquez
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia. Electronic address: rebecca.yao@griffithuni.edu.au.
authors.forename: Rebecca-Qing
authors.initials: RQ
authors.lastname: Yao
authors.affiliation: Universidad Autónoma de Madrid, Madrid, Spain. Electronic address: filip.lim@uam.es.
authors.forename: Filip
authors.initials: F
authors.lastname: Lim
authors.affiliation: Research Center for Materials Science, Nagoya University, Nagoya, Japan. Electronic address: hanc@cic.nagoya-u.ac.jp.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Han
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan. Electronic address: ojika@agr.nagoya-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ojika
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia; School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia. Electronic address: jenny.ekberg@qut.edu.au.
authors.forename: Jenny A K
authors.initials: JA
authors.lastname: Ekberg
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia. Electronic address: r.quinn@griffith.edu.au.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia. Electronic address: j.stjohn@griffith.edu.au.
authors.forename: James A St
authors.initials: JA
authors.lastname: John
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology*; D012503:Saponins / Q000494:pharmacology*
chemical_list: D012503:Saponins; C470915:linckoside A; C470916:linckoside B; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Glia; Natural compound; Neural regeneration; Starfish; Transplantation