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SAT0005 A Meta-Analysis and A Functional Study with Transmitochondrial Cybrids Confirm The Role of The Mtdna Haplogroups in The Development of Incident Knee Osteoarthritis. Data from Check and Oai

2016; BMJ; Volume: 75; Issue: Suppl 2 Linguagem: Inglês

10.1136/annrheumdis-2016-eular.5893

1468-2060

Ignacio Rego‐Pérez, M. Fernández-Moreno, Angel Soto‐Hermida, M.E. Vázquez-Mosquera, E. Cortés-Pereira, S. Relaño, Tamara Hermida‐Gómez, Sonia Pértega‐Díaz, N. Oreiro, C. Fernández-López, Rafael Garesse, Francisco J. Blanco,

Osteoarthritis Treatment and Mechanisms

Background In the last years the study of the mitochondria in the context of osteoarthritis (OA) attracted much attention. In the present work we aim to analyze the role of the mtDNA haplogroups in the development of incident knee OA in well-characterized study cohorts Objectives To analyze the influence of the mtDNA haplogroups in the rate of incident knee OA in the prospective cohorts of CHECK and OAI and to perform functional analysis with transmitochondrial cybrids to explore the consequences of the mitochondrial background in the pathogenesis of Osteoarthritis Methods The influence of the haplogroups in the development of incident knee OA at eight years in 2579 subjects from the Osteoarthritis Initiative (OAI) and 635 subjects from the Cohort hip and Cohort knee (CHECK) was assessed. A subsequent meta-analysis was conducted to strengthen the association of these individual studies. Transmitochondrial cybrids carrying the haplogroups J and H were constructed to study the influence of the mitochondrial background in different OA-related features. Results The haplogroup J significantly associates with a decreased risk of incident knee OA in subjects from the OAI (HR=0.680;95%CI=0.470–0.968;p<0.05) and CHECK (HR=0.728;95%CI=0.469–0.998;p<0.05). The subsequent meta-analysis including 3214 cases showed that the haplogroup J significantly associates with a lower risk of incident knee OA (HR=0.702;95%CI=0.541–0.912;p=0.008) (Figure 1). Compared with the haplogroup H, haplogroup J shows a lower free radical production, specially peroxide/peroxynitrite (52.51±11.34 vs 41.26±7.48;p<0.05) and superoxide (8.58±3.0 vs 4.25±0.9;p<0.05), a higher cell survival under oxidative stress conditions (29.63±3.3 vs 56.45±7.36;p<0.05), a lower grade of apoptosis (7.35±3.78 vs 4.69±1.68;p<0.05) as well as a lower expression of the mitochondrially-related pro-apoptotic gene BBC3 (3.3-fold;p<0.05), a higher lactate production (64.22±10.76mg/dl vs 51.42±6.85mg/dl;p<0.05) and a lower expression of the mitochondrial biogenesis-related gene PGC1-α (2-fold;p<0.05) Conclusions The haplogroup J reduces the risk of incident knee OA. This mitochondrial variant constitute a protective phenotype against the development of OA, emerging as a powerful OA biomarker and even leading to the consideration of the mitochondrion as a potential therapeutic target in OA Acknowledgement We9d like to acknowledge to the participants of CHECK and OAI cohorts Disclosure of Interest None declared