Beckmann Janet, Schubert Jan, Morhenn Hans-Georg, Grau Veronika, Schnettler Reinhard, Lips Katrin Susanne
Laboratory of Experimental Trauma Surgery, Justus-Liebig University, Schubert Strasse 81, 35392, Giessen, Germany.
Laboratory of Experimental Surgery, Justus-Liebig University, Giessen, German.
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.
越来越多的证据表明，非神经元胆碱能系统在类风湿性关节炎（RA）的病理过程中起重要作用。胆碱转运进入细胞是乙酰胆碱（ACh）合成的限速步骤，ACh可直接或通过囊泡从细胞中释放。然而，在人体关节中，关于胆碱的摄取或ACh从细胞中的释放知之甚少。因此，我们分析了骨关节炎（OA）和RA患者的人类髋关节滑膜和软骨中有机阳离子转运体（OCT）成员、新发现的胆碱转运体样（CTL）家族成员以及经典神经元成分如高亲和力胆碱转运体（CHT1）和囊泡ACh转运体（VAChT）的表达。OCT1、OCT3和OCTN1以及CTL家族的所有成员在滑膜和软骨样本中均有表达。CTL1和CTL2的表达定位于滑膜巨噬细胞和成纤维细胞中。仅在滑膜中可检测到CHT1 mRNA表达，而在所有样本中均完全未检测到VAChT。因此，在人体关节中，胆碱转运进入细胞和ACh的释放似乎主要由OCT和CTL家族成员介导。转运体的表达似乎不受病理状态的影响，因为在OA或RA患者的关节之间未检测到差异。然而，重要的是，人体关节中存在胆碱摄取和非神经元ACh释放的所有必要成分。
