SAT0561 Mitochondrial background influences the joint evolution in a conplastic mouse model of ageing

Background Several studies showed interesting associations between mtDNA haplogorups and different OA-related features, including prevalence, incidence or progression of the disease1–3. The use of conplastic animals-individuals with the same nuclear genome but different mtDNA variants-provides an accurate tool to study the influence of the mitochondrial background in the ageing process4. Objectives To study the influence of mtDNA variation in the degree of joint deterioration of the knees of aged animals using a conplastic mouse model of ageing Methods mtDNAs from C57BL/6 and NZB/OlaHsd mice were used. These mtDNAs differ by 12 missense mutations, 4 tRNAs mutations, 8rRNAs mutations and 10 non-coding region mutations. Then, a conplastic mice strain was developed with the C57BL/6 nuclear genome and the NZB/OlaHsd mtDNA (BL/6NZB) to compare with the original C57BL/6 strain (BL/6C57) in animals of 25 and 75 weeks. A total of 38 limbs from 19 mice were processed to perform histologic analyses: 8 BL/6NZB25 w, 10 BL/6NZB75 w, 10 BL/6C5725 w and 10 BL/6C5775 w. Results Mankin score data showed significantly increased values in all knees from both strains at 75 w compared with 25 w (p The width of the epiphyseal plate was analysed in both tibia and femur bones. The results showed significantly decreased values in BL/6C57 at 75 w compared with the same strain at 25 w in tibial plateau (p Conclusions This study demonstrates the functional impact of mtDNA variation in the process of joint deterioration associated to ageing, leading to consider the mtDNA as a potential therapeutic target in osteoarthritis associated to ageing References [1] Shen, et al. PLoS One2014;9(10):e108896. [2] Fernandez-Moreno, et al. Ann Rheum Dis2017;76(6):1114–1122. [3] Fernandez-Moreno, et al. Rheumatology2017;56(2):263–270. [4] Latorre-Pellicer, et al. Nature2016;535(7613):561–5. Disclosure of Interest None declared