Expression of the non-neuronal cholinergic system in human knee synovial tissue from patients with rheumatoid arthritis and osteoarthritis

Schubert, Jan; Beckmann, Janet; Hartmann, Sonja; Morhenn, Hans-Georg; Szalay, Gabor; Heiß, Christian; Schnettler, Reinhard; Lips, Katrin Susanne

doi:10.1016/j.lfs.2012.04.032

Cited by 17 publications

(11 citation statements)

References 21 publications

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“…ChAT mRNA and protein were localized to fibroblast-like and macrophage-like cells as well as to some extent in blood vessel walls of the synovial sample, while α 7 -nAChR was mostly found in the synovial intimal lining layer [197]. Recently, our group could show that different nAChR and mAChR as well as CarAT, transporters, and ACh-degrading enzymes are present in the synovial tissue of the human joint [198]. …”

Section: Musculoskeletal Systemmentioning

confidence: 99%

The Non-Neuronal Cholinergic System in Health and Disease

Beckmann¹,

Lips²

2013

Pharmacology

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102

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Acetylcholine (ACh) is not only a neurotransmitter but is an ancient molecule that can be released by and act on non-neuronal cells. In these cells the system of ACh-synthesizing enzymes, transporters, receptors and degrading enzymes is termed the non-neuronal cholinergic system (NNCS). There is increasing evidence that the NNCS is dysregulated in various diseases and can have an influence on their pathology. However, for many organ systems not much is known about the expression and function of the NNCS. Thus, this review focusses on the role of the NNCS in different organ systems in health and disease. Dysregulation of ACh synthesis and release, mutations or polymorphisms in genes encoding NNCS components, and auto-antibodies against NNCS components are common factors influencing disease progression. Pharmacological agents targeting the NNCS are already successfully in clinical use for some disorders, indicating that interfering with this system is very promising and more research is needed to elucidate the role of the NNCS in different tissues and pathological states.

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Section: Musculoskeletal Systemmentioning

confidence: 99%

The Non-Neuronal Cholinergic System in Health and Disease

Beckmann¹,

Lips²

2013

Pharmacology

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102

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“…Grimsholm et al in 2008 were able to show the expression of ChAT and the α7 nicotinic receptor in synovial tissue of the human knee joint in patients with RA and osteoarthritis (OA). A study of our own group confirmed the expression of α7 nicotinic receptor, other subunits of nicotinic receptors and various isotypes of muscarinic receptors (Schubert et al 2012 ) even though we could not clearly determine the mRNA expression of ChAT, the ACh-synthsizing enzyme CarAT was clearly detectable. With regard to choline and ACh transporters, we could further identify the expression of OCT1 and OCT3 in the synovial tissue of the knee joints of RA and OA patients.…”

Section: Introductionmentioning

confidence: 66%

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

et al. 2014

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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.

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“…An exciting body of research is the non-neuronal production and action of Ach: many non-neuronal cells are able to produce Ach and may express the nicotinic or muscarinic receptor, thereby allowing for a local autocrine or paracrine action of Ach. Thus, ChAT is expressed by the synovial membrane, but the cell type that secretes ChAT and whether Ach is produced because of this synovial ChAT remain unclear [17,72]. Synoviocytes and macrophages express a range of nicotinic subunits including alpha-7 homopentamer [16,73,74].…”

Section: Pns and Synoviummentioning

confidence: 99%

“…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.…”

Section: Pns and Synoviummentioning

confidence: 99%

“…Furthermore, most resident cells of osteoarticular tissue have receptors for sympathetic and parasympathetic neurotransmitters and thus may respond to their stimuli. Ach and norepinephrine (NE), as major parasympathetic and sympathetic mediators, respectively, could be produced locally by non-neuronal cells and therefore affect joint tissue homeostasis regardless of autonomic innervation [12,16,17]. In addition, despite its lack of innervation, the cartilage may be affected by catecholaminergic and cholinergic mediators, produced locally in the bone or synovium, because chondrocytes express most of their receptors.…”

Section: Introductionmentioning

confidence: 99%

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Role of the autonomic nervous system in osteoarthritis

Courties

Sellam

Bérenbaum

2017

Best Practice & Research Clinical Rheumatology

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a b s t r a c tJoint homeostasis is affected by local and systemic processes. Catecholaminergic and cholinergic fibers innervate the synovium, trabecular bone, and periosteum. Several studies have investigated the involvement of the autonomic nervous system (ANS) in joint homeostasis and the pathophysiology of osteoarthritis (OA). Various resident cells of osteoarticular tissues express receptors for sympathetic and parasympathetic neurotransmitters (norepinephrine/epinephrine and acetylcholine, respectively), which enables them to respond to autonomic stimuli. Furthermore, some of these cells are also able to synthesize neurotransmitters locally and secrete them, which may then act locally regardless of autonomic innervation. The sympathetic nervous system (SNS) is known for promoting bone loss, which has also been demonstrated in the subchondral bone during OA. However, it could interfere with other mechanisms in joint homeostasis. Indeed, intake of beta-blockers decreases pain sensation in individuals with OA; hence, the SNS could be one of the systemic links between hypertension and OA. Parasympathetic fibers may also be implicated in joint homeostasis and local control of inflammation. The vagus nerve has been found to have a strong antiinflammatory action in other rheumatic diseases through the nicotinic alpha-7 receptor, which is locally expressed by most joint

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Expression of the non-neuronal cholinergic system in human knee synovial tissue from patients with rheumatoid arthritis and osteoarthritis

Cited by 17 publications

References 21 publications

The Non-Neuronal Cholinergic System in Health and Disease

The Non-Neuronal Cholinergic System in Health and Disease

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

Role of the autonomic nervous system in osteoarthritis

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