PMID- 22715356
OWN - NLM
STAT- MEDLINE
DCOM- 20121018
LR  - 20220331
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 5
DP  - 2012
TI  - ATP induced brain-derived neurotrophic factor expression and release from 
      osteoarthritis synovial fibroblasts is mediated by purinergic receptor P2X4.
PG  - e36693
LID - 10.1371/journal.pone.0036693 [doi]
LID - e36693
AB  - Brain-derived neurotrophic factor (BDNF), a neuromodulator involved in 
      nociceptive hypersensitivity in the central nervous system, is also expressed in 
      synoviocytes of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. We 
      investigated the role of P2 purinoreceptors in the induction of BDNF expression 
      in synovial fibroblasts (SF) of OA and RA patients. Cultured SF from patients 
      with symptomatic knee OA and RA were stimulated with purinoreceptor agonists ATP, 
      ADP, or UTP. The expression of BDNF mRNA was measured by quantitative TaqMan PCR. 
      BDNF release into cell culture supernatants was monitored by ELISA. P2X4 
      expression in synovial tissue was detected by immunohistochemistry. Endogenous 
      P2X4 expression was decreased by siRNA transfection before ATP stimulation. 
      Kinase pathways were blocked before ATP stimulation. BDNF mRNA expression levels 
      in OASF were increased 2 h and 5 h after ATP stimulation. Mean BDNF levels in 
      cell culture supernatants of unstimulated OASF and RASF were 19 (+/-9) and 67 (+/-49) 
      pg/ml, respectively. BDNF levels in SF supernatants were only elevated 5 h after 
      ATP stimulation. BDNF mRNA expression in OASF was induced both by P2X receptor 
      agonists ATP and ADP, but not by UTP, an agonist of P2Y purinergic receptors. The 
      ATP-induced BDNF mRNA expression in OASF was decreased by siRNA-mediated 
      reduction of endogenous P2X4 levels compared to scrambled controls. Inhibition of 
      p38, but not p44/42 signalling reduced the ATP-mediated BDNF mRNA induction. Here 
      we show a functional role of the purinergic receptor P2X4 and p38 kinase in the 
      ATP-induced expression and release of the neurotrophin BDNF in SF.
FAU - Klein, Kerstin
AU  - Klein K
AD  - Center of Experimental Rheumatology, Division of Rheumatology and Institute of 
      Physical Medicine, University Hospital Zurich, Zurich, Switzerland.
FAU - Aeschlimann, Andre
AU  - Aeschlimann A
FAU - Jordan, Suzana
AU  - Jordan S
FAU - Gay, Renate
AU  - Gay R
FAU - Gay, Steffen
AU  - Gay S
FAU - Sprott, Haiko
AU  - Sprott H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120525
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Purinergic P2X4)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - UT0S826Z60 (Uridine Triphosphate)
SB  - IM
MH  - Adenosine Diphosphate/pharmacology
MH  - Adenosine Triphosphate/*pharmacology
MH  - Arthritis, Rheumatoid/metabolism
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cells, Cultured
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fibroblasts/*drug effects/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Osteoarthritis/*metabolism
MH  - Polymerase Chain Reaction
MH  - RNA, Small Interfering
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Purinergic P2X4/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Synovial Membrane/*cytology
MH  - Uridine Triphosphate/pharmacology
PMC - PMC3360754
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/06/21 06:00
MHDA- 2012/10/19 06:00
PMCR- 2012/05/25
CRDT- 2012/06/21 06:00
PHST- 2011/11/01 00:00 [received]
PHST- 2012/04/10 00:00 [accepted]
PHST- 2012/06/21 06:00 [entrez]
PHST- 2012/06/21 06:00 [pubmed]
PHST- 2012/10/19 06:00 [medline]
PHST- 2012/05/25 00:00 [pmc-release]
AID - PONE-D-11-21635 [pii]
AID - 10.1371/journal.pone.0036693 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(5):e36693. doi: 10.1371/journal.pone.0036693. Epub 2012 May 25.