Expression of choline and acetylcholine transporters in synovial tissue and cartilage of patients with rheumatoid arthritis and osteoarthritis

Cell Tissue Res. 2015 Feb;359(2):465-477. doi: 10.1007/s00441-014-2036-0. Epub 2014 Nov 25.


Increasing evidence is showing that the non-neuronal cholinergic system plays an important role in the pathology of rheumatoid arthritis (RA). Choline transport into the cell is the rate-limiting step for the synthesis of acetylcholine (ACh), which can be released directly or in vesicles from the cell. However, in the human joint little is known about choline import or the release of ACh from the cell. Thus, we analyze the expression of members of the organic cation transporter (OCT), of the newly discovered choline transporter-like (CTL) family and of classical neuronal components such as the high-affinity choline transporter (CHT1) and the vesicular ACh transporter (VAChT) in the synovium and cartilage of the human hip joint from patients with osteoarthritis (OA) and RA. OCT1, OCT3 and OCTN1 and all members of the CTL family were expressed in synovial and cartilage samples. The expression of CTL1 and CTL2 was localized in synovial macrophages and fibroblasts. CHT1 mRNA expression was detectable only in the synovium, whereas VAChT was completely absent in all samples. Therefore, in the human joint, choline transport into the cell and the release of ACh seems to be mediated mainly by members of the OCT and CTL family. Expression of transporters appears not to be influenced by the pathological state, as no differences have been detected between joints from OA or RA patients. Importantly, however, all necessary components for choline import and the release of non-neuronal ACh are present in the human joint.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / pathology
  • Cartilage / metabolism*
  • Cartilage / pathology
  • Choline / metabolism*
  • Endothelial Cells / metabolism
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Macrophages / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Neurons / metabolism
  • Osteoarthritis / genetics
  • Osteoarthritis / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Synovial Membrane / metabolism*


  • Membrane Transport Proteins
  • RNA, Messenger
  • Choline
  • Acetylcholine