Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: The study of the mitochondria in the context of osteoarthritis (OA) attracted much attention. In this study we aimed to evaluate the influence of the mitochondrial DNA haplogroups in the risk of incident knee OA and to explain the functional consequences of this association to identify potential therapeutic targets.
Methods: The influence of the haplogroups in the rate 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. Incident knee OA was defined as a new onset KL grade ≥ 2 during 96 months follow-up. Finally, a subsequent meta-analysis was conducted to synthetize results. Transmitochondrial cybrids carrying the haplogroups J and H were constructed to study the influence of the mitochondrial background in different OA-related features using an extracellular flux analyzer
Results: The haplogroup J 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 associates with a lower risk of incident knee OA (HR=0.702; 95% CI=0.541-0.912; P=0.008) (Figure 1). Cybrids with the haplogroup H show higher mitochondrial respiration and glycolysis leading to an increased ATP production. On the contrary, haplogroup J shows a significantly lower free radical production, higher cell survival under oxidative stress conditions and lower grade of apoptosis as well as lower expression of the mitochondrially-related pro-apoptotic gene BBC3
Conclusion: The haplogroup J reduces the risk of incident knee OA. This mitochondrial variant constitutes a protective phenotype against the development of OA and his beneficial physiological effects could be emulated to identify potential therapeutic targets to treat OA.
To cite this abstract in AMA style:Rego-Pérez I, Fernandez Moreno M, Soto-Hermida A, Vazquez Mosquera ME, Cortés-Pereira E, Relaño-Fernandez S, Hermida-Gómez T, Pertega S, Garesse R, Oreiro N, Fernandez-Lopez C, Blanco FJ. A Replication Study and Meta-Analysis Demonstrate the Influence of the mtDNA Haplogroups in the Rate of Incident Knee Osteoarthritis. Functional Explanation of This Association Using Transmitochondrial Cybrids [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/a-replication-study-and-meta-analysis-demonstrate-the-influence-of-the-mtdna-haplogroups-in-the-rate-of-incident-knee-osteoarthritis-functional-explanation-of-this-association-using-transmitochondria/. Accessed October 16, 2021.
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