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AB0109 Increased Subchondral Bone Resorption in the Absence of Osteoarthritis in a Mtdna Mutator Mouse Model of Premature Aging
  1. J. Geurts1,
  2. P. Distel1,
  3. M. Müller-Gerbl2,
  4. T.A. Prolla3,
  5. G. Kujoth4,
  6. U.A. Walker5,
  7. T. Hügle1,5
  1. 1Osteoarthritis Research Center, University Hospital Basel
  2. 2Institute of Anatomy, University Basel, Basel, Switzerland
  3. 3Laboratory of Genetics
  4. 4Department of Neurological Surgery, University of Wisconsin, Madison, United States
  5. 5Rheumatology, University Hospital Basel, Basel, Switzerland

Abstract

Background Age is the most prominent risk factor for osteoarthritis and mitochondrial DNA dysfunction has been repeatedly described in human osteoarthritic chondrocytes. Mice expressing a proofreading-deficient mitochondrial DNA polymerase (POLG) mutant accumulate an excess of reactive oxygen species and apoptosis and develop a premature aging phenotype. While these mice display a reduction in bone density, it is unclear whether they are more prone to developing osteoarthritis.

Objectives In this study, we assessed the histomorphometric properties of subchondral bone and cartilage tissues in premature aging mice.

Methods Mice carrying heterozygous (wt/mut n=5) or homozygous (mut/mut n=4) D257A mutations in POLG were compared with wildtype littermates (wt n=7). Animals were aged between eleven and fifteen months. Sagittal histological sections from knee joints were stained with Safranin-O/Fast Green and cartilage degeneration was assessed using OARSI scores. Subchondral bone area fraction (B.Ar/T.Ar) and osteoclast numbers (Oc.N/mm perimeter) between epiphyses and articular cartilage was determined on tissues stained for tartrate-resistant acid phosphatase (TRAP) and methylene blue using bone histomorphometric analyses.

Results Wild type mice revealed only low grade cartilage degeneration (OARSI score <1), predominantly loss of cartilage proteoglycans. OARSI scores were found to be equally low in wt/mut and mut/mut mice, showing no statistical differences between groups. Notably, subchondral bone area fraction was significantly decreased in mut/mut (0.20±0.1) compared with wt/mut (0.42±0.03) and wt (0.45±0.04) animals. Correspondingly, Oc.N per mm subchondral bone surface were strongly increased (p<0.05) between mut/mut (0.88±0.30) and wt/mut (0.25±0.03) and wt (0.12±0.04) mice.

Conclusions Mice with premature aging due to accumulation of mtDNA mutations display increased bone remodelling favouring subchondral bone resorption. Additional biomechanical factors might be required in this premature aging phenotype for development of osteoarthritis.

Disclosure of Interest None declared

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