03/12-2019 : Chunyi Wen : Hypertension meets osteoarthritis: a revisit to vascular aetiology

02 - Décembre - 2019

LES LUNDIS DE SAINT-ANTOINE

Bâtiment Kourilsky - 18h

Salle des Conférences (Rez de Chaussée),

184 rue du Faubourg Saint-Antoine, Paris

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MARDI 03 DECEMBRE 2019

Hypertension meets osteoarthritis: a revisit to vascular aetiology

Chunyi Wen

Dr. Chunyi Wen, Ass Prof, Department of biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong

Invité par l’Equipe F.Berenbaum

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Vascular aetiology of osteoarthritis (OA) has been proposed for decades. It was once postulated that subchondral bone ischaemia, e.g. in hypertension, might jeopardize the gas and nutrition exchange in bone-cartilage functional unit, and ultimately contributes to destruction of entire joint in the pathogenesis of OA. However, the exact mechanism remains poorly understood until now. Blood pressure has been causally associated with the risk of OA, yet the existing evidences are contradicting. Therefore, we included total 22 clinical studies with 85,455 participants for systemic review and meta-analysis. The overall likelihood of having OA significantly increased in the people with hypertension compared to the normotensive subjects. The association of hypertension with OA was detected in knee not in hand. Moreover, there existed a stronger association of hypertension with radiographic knee OA than symptomatic knee OA. We deployed a machine learning approach in an attempt to develop a patient-specific predictive model for the progression of radiographic knee OA using the database of FNIH OA biomarker consortium. In addition to demographic and radiographic features, metabolic components such as mean artery pressure, the difference between systolic and diastolic blood pressure, have been enrolled in the best performance predictive models. To better understand the molecular mechanism underlying hypertension and OA, we examined three animal models of hypertension, including spontaneous hypertensive rat (SHR) model, DOCA-salt hypertensive rat model, and transgenic endothelial endothelin-1 overexpressed (TET-1) mouse model. SHR and DOCA models are characterized by activation of renin-angiotensin system for vasoconstriction, exhibiting p16+ senescent cells (SnCs) accumulation not only in endothelium but also in bone and joint. Captopril, an angiotensin converting enzyme inhibitor for lowing blood pressure, could reduce SnCs in endothelium, bone and cartilage. In TET-1 mice, we observed oxidative stress and SnCs accumulation with OA-like phenotypes development. TET-1 exhibited more ETBR and fewer ETAR expression in articular cartilage compared to their wildtype littermates. In a well-received DMM model, we firstly delineated upregulation of ETBR together with oxidative damage occurred prior to SnCs accumulation and cartilage degradation. Selective blockade of ETBR but not ETAR alleviated oxidative stress, removed SnCs and ameliorate cartilage loss after DMM. Our findings shed the light on a crucial role of the ET-1-ETBR axis, the key vascular tone regulator, in the pathogenesis of OA

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