title: GDNF From Human Periodontal Ligament Cells Treated With Pro-Inflammatory Cytokines Promotes Neurocytic Differentiation of PC12 Cells.
abstract: Glial cell line-derived neurotrophic factor (GDNF) is known to mediate multiple biological activities such as promotion of cell motility and proliferation, and morphogenesis. However, little is known about its effects on periodontal ligament (PDL) cells. Recently, we reported that GDNF expression is increased in wounded rat PDL tissue and human PDL cells (HPDLCs) treated with pro-inflammatory cytokines. Here, we investigated the associated expression of GDNF and the pro-inflammatory cytokine interleukin-1 beta (IL-1β) in wounded PDL tissue, and whether HPDLCs secrete GDNF which affects neurocytic differentiation. Rat PDL cells near the wounded area showed intense immunoreactions against an anti-GDNF antibody, where immunoreactivity was also increased against an anti-IL-1β antibody. Compared with untreated cells, HPDLCs treated with IL-1β or tumor necrosis factor-alpha showed an increase in the secretion of GDNF protein. Conditioned medium of IL-1β-treated HPDLCs (IL-1β-CM) increased neurite outgrowth of PC12 rat adrenal pheochromocytoma cells. The expression levels of two neural regeneration-associated genes, growth-associated protein-43 (Gap-43), and small proline-rich repeat protein 1A (Sprr1A), were also upregulated in IL-1β-CM-treated PC12 cells. These stimulatory effects of IL-1β-CM were significantly inhibited by a neutralizing antibody against GDNF. In addition, U0126, a MEK inhibitor, inhibited GDNF-induced neurite outgrowth of PC12 cells. These findings suggest that an increase of GDNF in wounded PDL tissue might play an important role in neural regeneration probably via the MEK/ERK signaling pathway. J. Cell. Biochem. 118: 699-708, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Endodontology, Kyushu University Hospital, Maidashi, Higashi-ku, Fukuoka, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Section of Endodontology & Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Division of General Oral Care, Kyushu University Hospital, Maidashi, Higashi-ku, Fukuoka, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Wada
authors.affiliation: Department of Endodontology, Kyushu University Hospital, Maidashi, Higashi-ku, Fukuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tomokiyo
authors.affiliation: Department of Endodontology, Kyushu University Hospital, Maidashi, Higashi-ku, Fukuoka, Japan.
authors.forename: Daigaku
authors.initials: D
authors.lastname: Hasegawa
authors.affiliation: OBT Research Center, Faculty of Dental Science, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Hamano
authors.affiliation: Section of Endodontology & Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mitarai
authors.affiliation: Section of Endodontology & Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Monnouchi
authors.affiliation: Section of Endodontology & Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Yuda
authors.affiliation: Department of Endodontology, Kyushu University Hospital, Maidashi, Higashi-ku, Fukuoka, Japan.|Section of Endodontology & Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Maeda
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D019922:GAP-43 Protein / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D010513:Periodontal Ligament / Q000166:cytology / Q000293:injuries / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D016207:Cytokines; D019922:GAP-43 Protein; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR; NERVE REGENERATION; NEURAL-LIKE PC12 CELL; PERIODONTAL LIGAMENT CELL