SAT0071 Subchondral osteopenia but not cartilage damage is prevalent in knee joints of prematurely ageing mitochondrial dna mutator mice

Background Mitochondrial dysfunction has been demonstrated in ageing and osteoarthritic tissues. However it remains unclear whether dysfunctional mitochondria are directly implied in the pathogenesis of osteoarthritis. Objectives We investigated knee joints of prematurely ageing mitochondrial DNA mutator mice ( Polg D275A ) to evaluate a causal relationship between mitochondrial dysfunction and different features of osteoarthritis. Methods Bone structural parameters and chondropathy were evaluated in knee joints of mice displaying increased mtDNA mutations rates and accelerated ageing, due to expression of a proofreading-deficient mtDNA polymerase, using micro-computed tomography and histopathological analysis. Results Homozygous mutants displayed osteopenia of the epiphyseal trabecular bone and subchondral cortical plate in comparison to wild type controls and heterozygous mutants. Osteopenia was associated with a strong increase of osteoclast numbers (0.88±0.30/mm bone perimeter) compared to heterozygous (0.25±0.03/mm) and wild type mice (0.12±0.04/mm). New bone formation was not observed. Wild type mice displayed only low grade cartilage degeneration (OARSI grade ≤1) due to loss of cartilage proteoglycans. Increased tibio-femoral chondropathy was not apparent in hetero- and homozygous mitochondrial DNA mutator mice. Conclusions Mitochondrial dysfunction and premature ageing in mice with somatically acquired mtDNA mutations predisposes to enhanced subchondral bone resorption as potential early step of osteoarthritis, but not to cartilage damage or new bone formation. This phenotype potentially corresponds to an osteoporotic osteoarthritis phenotype in humans. Disclosure of Interest None declared