title: Expression of the non-neuronal cholinergic system in human knee synovial tissue from patients with rheumatoid arthritis and osteoarthritis.
abstract: OBJECTIVE
  As the stimulation of the α7-nicotinic acetylcholine receptor (nAChR), which is present in the synovium of patients with rheumatoid arthritis (RA), leads to a decrease in pro-inflammatory cytokines, the α7-nAChR is being discussed as a new therapeutic target. On this background we addressed the question whether α7-nAChR mRNA was differentially expressed in RA compared to osteoarthritis (OA) synovial samples and whether other components of the non-neuronal cholinergic system were also present and differentially expressed in the synovium of patients with RA in comparison to OA.
  
  
  METHODS
  The expression of nicotinic and muscarinic acetylcholine receptors (mAChRs), choline and acetylcholine transporters, synthesising and degrading enzymes was determined in human samples of synovial tissue from patients with RA and OA using RT-PCR and immunofluorescence labelling.
  
  
  RESULTS
  Compared to OA, patients with RA showed increased expression of nAChR subunit β4 while a decline in subunits α2 and α4 as well as in mAChR M1R was observed. For all other nAChR subunits and mAChRs however there was no significant difference between RA and OA patients. With regard to the ACh transporters and enzymes no expressional changes were observed between OA and RA patients, except for the choline acetyltransferase (ChAT) which was only detected in OA but not in RA synovium.
  
  
  CONCLUSIONS
  Our results indicate that besides α7-nAChR other components of the non-neuronal cholinergic system are present and differentially expressed in the synovium of RA and OA patients, which makes them interesting alternative targets in the development of new strategies for RA therapy.
authors.affiliation: Laboratory for Experimental Trauma Surgery, Justus-Liebig University, Giessen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Schubert
authors.forename: Janet
authors.initials: J
authors.lastname: Beckmann
authors.forename: Sonja
authors.initials: S
authors.lastname: Hartmann
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Morhenn
authors.forename: Gabor
authors.initials: G
authors.lastname: Szalay
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schnettler
authors.forename: Katrin Susanne
authors.initials: KS
authors.lastname: Lips
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007719:Knee Joint / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011976:Receptors, Muscarinic / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D000109:Acetylcholine