mtDNA Cybrids from OA Patients Are Less Efficient Using Glycolysis and Are More Susceptible to Apoptosis Under Stress Conditions

Mercedes Fernandez Moreno^1,2, Tamara Hermida-Gómez³, Andrea Dalamao-Fernandez⁴, M. Eugenia Vazquez Mosquera⁴, Estefanía Cortés-Pereira¹, Morena Scotece⁴, Sara Relaño-Fernandez⁵, Ignacio Rego-Pérez¹ and Francisco J Blanco⁶, ¹Servicio de Reumatología. Area Genomica. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain, ²CIBER-BBM, Madrid, Spain, ³Rheumatology, INIBIC. Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. CIBER-BBN., A Coruña, Spain, ⁴Servicio de Reumatología. Area Genomica. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A CORUÑA, Spain, ⁵Plataforma de Genómica. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain, ⁶Servicio de Reumatología. Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC). As Xubias, 15006. A Coruña. España, A Coruña, Spain

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Apoptosis, Mitochondria, osteoarthritis and stress

Session Information

Date: Monday, November 6, 2017

Title: Genetics, Genomics and Proteomics Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Previous studies have showed that chondrocytes from OA patients had mitochondrial alteration in comparison with healthy. However the role of mitochondria in the biological dysfunction of chondrocytes is not totally know. Cybrids are optimal cellular models to study mitochondrial biology and function implications in the cellular behavior, since they carry different mitochondrial variants with the same nuclear background, excluding the variations because of nuclear genome. Purppose: To test the real role of mitochondrial function in OA pathogenesis using mtDNA cybrids.

Methods: mtDNA Cybrids were developed using the cell line 143B.TK^– Rho-0 as the nuclear donor, and platelets from patients without and with knee osteoarthritis respectively as mitochondrial donors (N vs OA). The stress response was evaluated analyzed O₂^– production; percentage of cell survival in presence of H₂O₂ and the level of apoptotic cells were studied using flow cytometry. The OXPHOS function and glycolytic activity was evaluated by SeaHorse XFp. The metabolic status was evaluated by glucose consumption and lactic acid production.

Results: Cybrids carrying the platelets from OA patients showed significant higher levels O₂^– than N (36.61% vs 17.79%). Percentage of not viable cell in presence of H₂O₂ was higher in OA than in N cybrids (40.1 % vs 27.15 %,). The percentage of cell in inducing apoptosis condition was higher in OA than in N cybrids (15.68% vs 6.41%). OA cybrids had lower basal respiration (92.07 and 155.5), and maximal respiratory capacity (114.7 and 160.6) than N. The analysis of ATP production was lower in OA than in N cybrids (66.69 vs 101.5). The % spare respiratory capacity for the N was significantly lower than in OA cybrids (107 vs 124.7). Cybrids carrying the mtDNA from OA patients showed higher glucose consumption than N cybrids (43.77 mg/ml vs 31.91 mg/ml) however in the lactic acid production did not exit differences. The glycolytic showed that OA cybrids had lower glycolysis (71.05 vs 85.43) but higher glycolytic reserve than N cybrids (56.60 vs 39.73).

Conclusion: These results showed that the mitochondria obtained from healthy and OA donors had a different behaviour and offer a real rationale for why mitochondria alterations play an important role in OA pathogenesis.

Disclosure: M. Fernandez Moreno, None; T. Hermida-Gómez, None; A. Dalamao-Fernandez, None; M. E. Vazquez Mosquera, None; E. Cortés-Pereira, None; M. Scotece, None; S. Relaño-Fernandez, None; I. Rego-Pérez, None; F. J. Blanco, Pfizer Inc, 5.

To cite this abstract in AMA style:

Fernandez Moreno M, Hermida-Gómez T, Dalamao-Fernandez A, Vazquez Mosquera ME, Cortés-Pereira E, Scotece M, Relaño-Fernandez S, Rego-Pérez I, Blanco FJ. mtDNA Cybrids from OA Patients Are Less Efficient Using Glycolysis and Are More Susceptible to Apoptosis Under Stress Conditions [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/mtdna-cybrids-from-oa-patients-are-less-efficient-using-glycolysis-and-are-more-susceptible-to-apoptosis-under-stress-conditions/. Accessed .

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