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

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00441-014-2036-0) contains supplementary material, which is available to authorized users.

Cholinergic Targets in Lung Cancer

“…In particular, Song et al [29] have demonstrated that knockdown of CTL4 in lung cancer cells decreases ACh synthesis while increasing expression of CTL4 increases choline transport and ACh synthesis. Besides CTL4, the organic cation transporter (OCT) 1 and 3 have also been linked to non-neuronal ACh synthesis, as demonstrated by expression in cell types that synthesize ACh but do not express CHT1 [30,31]. …”

Peptidomic analysis of cartilage and subchondral bone in OA patients

“…Peptide sequences from SLC18A3 were present in all six patients. Previous studies have shown that various choline and acetylcholine transporters are expressed in synovial tissue and cartilage from patients with rheumatoid arthritis and OA, however, SLC18A3 was absent …”

“…Previous studies have shown that various choline and acetylcholine transporters are expressed in synovial tissue and cartilage from patients with rheumatoid arthritis and OA, however, SLC18A3 was absent. 40 SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) is involved in synaptic plasticity through its regulation of NMDA receptors as well as regulating the spine. 41 SHANK2 endogenous peptide sequences were present in all six patients.…”

Role of the autonomic nervous system in osteoarthritis

“…Synoviocytes and macrophages express a range of nicotinic subunits including alpha-7 homopentamer [16,73,74]. The OA synovial membrane also expresses choline transporters and muscarinic receptors 1, 3, 4, and 5 and nicotinic subunits alpha-3, -5, -6, -7, -9, and -10 [17,75]. Therefore, the synovium may be able to produce and respond to Ach stimulation.…”