SAT0561 Mitochondrial background influences the joint evolution in a conplastic mouse model of ageing
Authors: I. Rego-Pérez, A.V. Lechuga-Vieco, M. Scotece, P. Filgueira-Fernández, S. Pértega, J.A. Enríquez, F.J. Blanco
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Several studies showed interesting associations between mtDNA haplogorups and different OA-related features, including prevalence, incidence or progression of the disease<sup>1–3</sup>. 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 process<sup>4</sup>. <h3>Objectives</h3> 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 <h3>Methods</h3> 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/6<sup>NZB</sup>) to compare with the original C57BL/6 strain (BL/6<sup>C57</sup>) in animals of 25 and 75 weeks. A total of 38 limbs from 19 mice were processed to perform histologic analyses: 8 BL/6<sup>NZB</sup>25 w, 10 BL/6<sup>NZB</sup>75 w, 10 BL/6<sup>C57</sup>25 w and 10 BL/6<sup>C57</sup>75 w. <h3>Results</h3> Mankin score data showed significantly increased values in all knees from both strains at 75 w compared with 25 w (p&lt;0,001), confirming the ageing of the joint. When 75 w mice were selected (table 1), the BL/6<sup>C57</sup> strain showed a significantly increased score in whole joint (p=0,038), femoral condyles (p=0,021) and medial femoral condyle (p=0,015) than BL/6<sup>NZB</sup> strain. Safranin-O/Fast-green ration value at 75 w was higher in the medial compartment of BL/6<sup>NZB</sup> compared with BL/6<sup>C57</sup> (both tibial plateau and femoral condyle); however, only the differences detected in the medial compartment of the tibial plateau reached the statistical significance (p&lt;0,001), whilst the differences detected in the femoral condyle borderline the statistical significance (p=0,091). The width of the epiphyseal plate was analysed in both tibia and femur bones. The results showed significantly decreased values in BL/6<sup>C57</sup> at 75 w compared with the same strain at 25 w in tibial plateau (p&lt;0,001) and femoral condyle (p=0,049); however, these differences were not observed in animals belonging to BL/6<sup>NZB</sup> strain. In addition, the BL/6<sup>C57</sup>75 w strain also showed significantly lower values in tibial plateau than BL/6<sup>NZB</sup> strain at the same age (p=0,032) <h3>Conclusions</h3> 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 <h3>References</h3> [1] Shen, et al. PLoS One2014;9(10):e108896. [2] Fernández-Moreno, et al. Ann Rheum Dis2017;76(6):1114–1122. [3] Fernández-Moreno, et al. Rheumatology2017;56(2):263–270. [4] Latorre-Pellicer, et al. Nature2016;535(7613):561–5. <h3>Disclosure of Interest</h3> None declared