17/10-2022 - Alice COURTIES : Involvement of cholinergic system in osteoarthritis and pain through the alpha 7 nicotinic acetylcholine receptor
12 - Octobre - 2022
LES LUNDIS DE SAINT-ANTOINE
Bâtiment Kourilsky - 13h–14h
Salle des Conférences (Rez de Chaussée),
184 rue du Faubourg Saint-Antoine, Paris
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LUNDI 17 OCTOBRE 2022
Involvement of cholinergic system in osteoarthritis and pain through the alpha 7 nicotinic acetylcholine receptor
Alice COURTIES
MCU-PH, CRSA, INSERM UMRS 938, Sorbonne Université, service de Rhumatologie, Hôpital Saint-Antoine, APHP, Paris
invitée par Equipe de Francis BERENBAUM, (Equipe BERENBAUM (francis.berenbaum@aphp.fr))
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Osteoarthritis (OA) is the most frequent joint disease characterized by joint pain and disability. It involves cartilage degradation, synovium inflammation and subchondral bone remodeling. Local low-grade inflammation plays a major role by triggering and perpetuating the disease. Beyond external risk factor of OA such as ageing or obesity, this study focused in possible endogenous protective factors. Acetylcholine (Ach) is produced and acts on both neuronal and non-neuronal cells through the nicotinic and muscarinic receptors. Beyond its role in autonomic function, Ach regulates inflammation and pain via the alpha 7 nicotinic Ach receptor (a7nAchR). Our work reveals that there is a local neuronal and non-neuronal cholinergic systems delivering potential Ach to joint tissues. Functional a7nAchR is expressed by cartilage and bone cells and its local activation decreases response to inflammatory stress. To the opposite its deletion aggravates cartilage lesions of OA. This suggests that a7nAchR is important for joint homeostasis and that its activation could be a promising target in OA. Indeed, preliminary data showed that systemic a7nAchR activation by vagal stimulation could decrease hand OA pain in human. However, a human-specific duplicate of the gene encoding for a7nAchR subunit (Chrna7) is responsible for a dominant negative protein called CHRFAM7A. Expression of CHRFAM7A in mice is associated with more severe OA and a decreased threshold of pain due to an inflammatory pattern in dorsal root ganglia and a decrease in agonist response. Altogether, this suggest strongly that cholinergic system is involved in OA pathophysiology and pain. The specific role of CHRFAM7A in human OA and pain must be elucidated.
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