PMID- 18390540
OWN - NLM
STAT- MEDLINE
DCOM- 20080715
LR  - 20211020
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 23
DP  - 2008 Jun 6
TI  - Brain-derived neurotrophic factor stimulates bone/cementum-related protein gene 
      expression in cementoblasts.
PG  - 16259-67
LID - 10.1074/jbc.M800668200 [doi]
AB  - Brain-derived neurotrophic factor (BDNF), recognized as essential in the 
      developing nervous system, is involved in differentiation and proliferation in 
      non-neuronal cells, such as endothelial cells, osteoblasts, and periodontal 
      ligament cells. We have focused on the application of BDNF to the regeneration of 
      periodontal tissue and indicated that BDNF promotes the regeneration of 
      experimentally created periodontal defects. Cementoblasts form cementum, 
      mineralized tissue, which is key to establishing a functional periodontium. The 
      application of BDNF to the regeneration of periodontal tissue requires 
      elucidation of the mechanism by which BDNF regulates the functions of 
      cementoblasts. In this study, we examined how BDNF regulates the mRNA expression 
      of bone/cementum-related proteins (alkaline phosphatase (ALP), osteopontin (OPN), 
      and bone morphogenetic protein-2 (BMP-2)) in cultures of immortalized human 
      cementoblast-like (HCEM) cells. BDNF elevated the mRNA levels of ALP, OPN, and 
      BMP-2 in HCEM cells. Small interfering RNA (siRNA) for TRKB, a high affinity 
      receptor of BDNF, siRNA for ELK-1, which is a downstream target of ERK1/2, and 
      PD98059, an ERK inhibitor, obviated the increase in the mRNA levels. BDNF 
      increased the levels of phosphorylated ERK1/2 and Elk-1, and the blocking of BDNF 
      signaling by treatment with siRNA for TRKB and PD98059 suppressed the 
      phosphorylation of ERK1/2 and Elk-1. Furthermore, BDNF increased the levels of 
      phosphorylated c-Raf, which activates the ERK signaling pathway. These findings 
      provide the first evidence that the TrkB-c-Raf-ERK1/2-Elk-1 signaling pathway is 
      required for the BDNF-induced mRNA expression of ALP, OPN, and BMP-2 in HCEM 
      cells.
FAU - Kajiya, Mikihito
AU  - Kajiya M
AD  - Department of Periodontal Medicine, Hiroshima University Graduate School of 
      Biomedical Sciences, Minami-ku, Hiroshima 34-8553, Japan.
FAU - Shiba, Hideki
AU  - Shiba H
FAU - Fujita, Tsuyoshi
AU  - Fujita T
FAU - Ouhara, Kazuhisa
AU  - Ouhara K
FAU - Takeda, Katsuhiro
AU  - Takeda K
FAU - Mizuno, Noriyoshi
AU  - Mizuno N
FAU - Kawaguchi, Hiroyuki
AU  - Kawaguchi H
FAU - Kitagawa, Masae
AU  - Kitagawa M
FAU - Takata, Takashi
AU  - Takata T
FAU - Tsuji, Koichiro
AU  - Tsuji K
FAU - Kurihara, Hidemi
AU  - Kurihara H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080403
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Bone and Bones/cytology/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism/*pharmacology
MH  - Cell Differentiation/drug effects/physiology
MH  - Cell Line, Transformed
MH  - Cell Proliferation/drug effects
MH  - Dental Cementum/cytology/*metabolism
MH  - Gene Expression Regulation/*drug effects/physiology
MH  - Humans
MH  - Nervous System/embryology
MH  - Organ Specificity/drug effects/physiology
MH  - Periodontal Ligament/cytology/*physiology
MH  - RNA, Messenger/biosynthesis
MH  - Regeneration/*drug effects/physiology
PMC - PMC3259653
EDAT- 2008/04/09 09:00
MHDA- 2008/07/17 09:00
PMCR- 2009/06/06
CRDT- 2008/04/09 09:00
PHST- 2008/04/09 09:00 [pubmed]
PHST- 2008/07/17 09:00 [medline]
PHST- 2008/04/09 09:00 [entrez]
PHST- 2009/06/06 00:00 [pmc-release]
AID - S0021-9258(20)46163-0 [pii]
AID - 16259 [pii]
AID - 10.1074/jbc.M800668200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Jun 6;283(23):16259-67. doi: 10.1074/jbc.M800668200. Epub 2008 
      Apr 3.