Role of the autonomic nervous system in osteoarthritis

Courties, Alice; Sellam, Jérémie; Bérenbaum, Francis

doi:10.1016/j.berh.2018.04.001

Cited by 42 publications

(30 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…nicotinic Ach and muscarinic receptors expressed by resident cells of the bone to exert anti-inflammatory effects, we wondered whether cholinergic nerves are locally expressed in subchondral bone 10,11 . Because it is challenging to characterize nerve structures using two-dimensional (2D) techniques with confocal microscopy, we adapted a recently published protocol for the three-dimensional (3D) analysis of immunofluorescence 12,13 .…”

mentioning

confidence: 99%

Clearing method for 3-dimensional immunofluorescence of osteoarthritic subchondral human bone reveals peripheral cholinergic nerves

Belle

Senay

Sautet

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

The cholinergic system plays a major anti-inflammatory role in many diseases through acetylcholine (Ach) release after vagus nerve stimulation. Osteoarthritis (OA) is associated with local low-grade inflammation, but the regulatory mechanisms are unclear. Local Ach release could have antiinflammatory activity since articular cells express Ach receptors involved in inflammatory responses. Using the 3DISCO clearing protocol that allows whole-sample 3-dimensional (3D) analysis, we cleared human OA cartilage-subchondral bone samples to search for cholinergic nerve fibres able to produce Ach locally. We analysed 3 plugs of knee cartilage and subchondral bone from 3 OA patients undergoing arthroplasty. We found no nerves in the superficial and intermediate articular cartilage layers, as evidenced by the lack of Peripherin staining (a peripheral nerves marker). Conversely, peripheral nerves were found in the deepest layer of cartilage and in subchondral bone. Some nerves in the subchondral bone samples were cholinergic because they coexpressed peripherin and choline acetyltransferase (ChAT), a specific marker of cholinergic nerves. However, no cholinergic nerves were found in the cartilage layers. It is therefore feasible to clear human bone to perform 3D immunofluorescence. Human OA subchondral bone is innervated by cholinergic fibres, which may regulate local inflammation through local Ach release. Osteoarthritis (OA) is the most common joint disease and is a considerable burden on quality of life due to joint pain, stiffness and loss of function 1. OA is mostly characterized by cartilage degradation but is now considered a whole-joint disease associated with subchondral bone remodelling and synovitis. Articular cartilage is composed of several layers, and the deepest layer, called calcified cartilage, is located on top of subchondral bone. Articular cartilage is a unique tissue that is not innervated or vascularized. Communication between subchondral bone and calcified cartilage is needed for cartilage homeostasis. Such communication is also involved in the OA process because of the circulation of soluble mediators from subchondral bone to cartilage undergoing alterations 2. Interplay between subchondral bone and deep cartilage may involve micro-cracks at the junction between the two tissues as well as neoangiogenesis of the calcified cartilage, which could be directly involved in OA pathophysiology 3-5. Additionally, neurogenesis may play a role in OA pathophysiology. Walsh and colleagues previously showed that during OA, peripheral sensory and sympathetic nerves grow in calcified cartilage and may be involved in OA pain 6,7. Beyond sensory mediators and sensory nerves, the parasympathetic system has been reported to have anti-inflammatory properties through the action of its mediator, acetylcholine (Ach), on nicotinic Ach receptors and, in particular, the alpha7 nicotinic receptor 8,9. Ach production is controlled by choline acetyltransferase (ChAT), which is mainly recognized as a marker of cholinergic nerves. Bec...

show abstract

mentioning

confidence: 99%

Clearing method for 3-dimensional immunofluorescence of osteoarthritic subchondral human bone reveals peripheral cholinergic nerves

Belle

Senay

Sautet

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our understanding of the role of the non-neuronal cholinergic system as a critical regulator of inflammation and immunity is growing but remains controversial and poorly investigated in OA pathophysiology (21,22). Here, we showed that human and murine chondrocytes are part of the non-neuronal cholinergic system allowing local autocrine/paracrine action of ACh on joint cells.…”

Section: Discussionmentioning

confidence: 89%

The Role of the Non‐neuronal Cholinergic System in Inflammation and Degradation Processes in Osteoarthritis

Courties

Leite

et al. 2020

Arthritis & Rheumatology

Self Cite

View full text Add to dashboard Cite

Objective The non‐neuronal cholinergic system represents non‐neuronal cells that have the biochemical machinery to synthetize de novo and/or respond to acetylcholine (ACh). We undertook this study to investigate this biochemical machinery in chondrocytes and its involvement in osteoarthritis (OA). Methods Expression of the biochemical machinery for ACh metabolism and nicotinic ACh receptors (nAChR), particularly α7‐nAChR, in human OA and murine chondrocytes was determined by polymerase chain reaction and ligand‐binding. We investigated the messenger RNA expression of the human duplicate α7‐nACh subunit, called CHRFAM7A, which is responsible for truncated α7‐nAChR. We assessed the effect of nAChR on chondrocytes activated by interleukin‐1β (IL‐1β) and the involvement of α7‐nAChR using chondrocytes from wild‐type (WT) and α7‐deficient Chrna7−/− mice. The role of α7‐nAChR in OA was explored after medial meniscectomy in WT and Chrna7−/− mice. Results Human and murine chondrocytes express the biochemical partners of the non‐neuronal cholinergic system and a functional α7‐nAChR at their cell surface (n = 5 experiments with 5 samples each). The expression of CHRFAM7A in human OA chondrocytes (n = 23 samples) correlated positively with matrix metalloproteinase 3 (MMP‐3) (r = 0.38, P < 0.05) and MMP‐13 (r = 0.48, P < 0.05) expression. Nicotine decreased the IL‐1β–induced IL‐6 and MMP expression, in a dose‐dependent manner, in WT chondrocytes but not in Chrna7−/− chondrocytes. Chrna7−/− mice that underwent meniscectomy (n = 7) displayed more severe OA cartilage damage (mean ± SD Osteoarthritis Research Society International [OARSI] score 4.46 ± 1.09) compared to WT mice that underwent meniscectomy (n = 9) (mean ± SD OARSI score 3.05 ± 0.9; P < 0.05). Conclusion The non‐neuronal cholinergic system is functionally expressed in chondrocytes. Stimulation of nAChR induces antiinflammatory and anticatabolic activity through α7‐nAChR, but the anticatabolic activity may be mitigated by truncated α7‐nAChR in human chondrocytes. In vivo experiments strongly suggest that α7‐nAChR has a protective role in OA.

show abstract

“…69 Moreover, the choline acetyltransferase (ChAT) is detected in OA synovium, which means that resident cells are capable of synthesizing and releasing ACh in situ without autonomic innervation. 68,70 These data suggest that CAP may act on OA simultaneously through the vagus nerve and ACh, and then play a role in inhibiting OA development.…”

Section: The Cap and Osteoarthritismentioning

confidence: 87%

“…67 Studies have observed that the autonomic nervous system (ANS) is involved in joint homeostasis and OA pathogenesis: the subchondral bone of OA patients has peripheral and cholinergic fibres, which innervate the synovium, trabecular bone and periosteum; and resident cells of osteoarticular tissue have receptors for ACh as chondrocytes express α7nAChR on their surfaces. 63,68,69 α7nAChR was detected in chondrocytes of OA patients, but the increased expression was not as significant as that of patients with RA; meanwhile, mRNA expression of CHRFAM7A-which is capable of pruning α7nAChR and associated with the cartilage degradation--was significantly higher than that of Chrna7, indicating that functions of the CAP are impaired in OA, and this hypothesis was confirmed as prognosis of Chrna7 −/− mice that underwent meniscectomy was observably lower than that of normal control mice that got the same operation. 69 Moreover, the choline acetyltransferase (ChAT) is detected in OA synovium, which means that resident cells are capable of synthesizing and releasing ACh in situ without autonomic innervation.…”

Section: The Cap and Osteoarthritismentioning

confidence: 99%

The role of the cholinergic anti‐inflammatory pathway in autoimmune rheumatic diseases

et al. 2021

Scand J Immunol

View full text Add to dashboard Cite

The cholinergic anti-inflammatory pathway (CAP) is a classic neuroimmune pathway, consisting of the vagus nerve, acetylcholine (ACh)-the pivotal neurotransmitter of the vagus nerve-and its receptors. This pathway can activate and regulate the activities of immune cells, inhibit cell proliferation and differentiation, as well as suppress cytokine release, thereby playing an anti-inflammatory role, and widely involved in the occurrence and development of various diseases; recent studies have demonstrated that the CAP may be a new target for the treatment of autoimmune rheumatic diseases. In this review, we will summarize the latest progress with the view of figuring out the role of the cholinergic pathway and how it interacts with inflammatory reactions in several autoimmune rheumatic diseases, and many advances are results from a wide range of experiments performed in vitro and in vivo.How to cite this article: Lv J, Ji X, Li Z, Hao H. The role of the cholinergic anti-inflammatory pathway in autoimmune rheumatic diseases.

show abstract

Role of the autonomic nervous system in osteoarthritis

Cited by 42 publications

References 81 publications

Clearing method for 3-dimensional immunofluorescence of osteoarthritic subchondral human bone reveals peripheral cholinergic nerves

Clearing method for 3-dimensional immunofluorescence of osteoarthritic subchondral human bone reveals peripheral cholinergic nerves

The Role of the Non‐neuronal Cholinergic System in Inflammation and Degradation Processes in Osteoarthritis

The role of the cholinergic anti‐inflammatory pathway in autoimmune rheumatic diseases

Contact Info

Product

Resources

About