Aim: The purpose of this study was to evaluate whether pharmacologic treatments or genotypes shown to prolong murine lifespan ameliorate the severity of age-associated osteoarthritis. Materials and Methods: Male UM-HET3 mice were fed diets containing 17-α-estradiol, acarbose, nordihydroguaiaretic acid, or control diet per the National Institute on Aging Interventions Testing Program (ITP) protocol. Findings were compared to genetically long-lived male Ames dwarf mice. Stifles were analyzed histologically with articular cartilage structure (ACS) and safranin O scoring as well as with quantitative histomorphometry. Results: Depending on the experimental group, ITP mice were between 450 and 1150 days old at the time of necropsy and 12–15 animals were studied per group. Two age groups (450 and 750 days) with 16–20 animals per group were used for Ames dwarf studies. No differences were found in the ACS or safranin O scores between treatment and control groups in the ITP study. There was high variability in most of the histologic outcome measures. For example, the older UM-HET3 controls had ACS scores of 6.1 ± 5.8 (mean±SD) and Saf O scores of 6.8 ± 5.6. Nevertheless, 17-α-estradiol mice had larger areas and widths of subchondral bone compared to controls, and dwarf mice had less subchondral bone area and width and less articular cartilage necrosis than non-dwarf controls. Conclusions: UM-HET3 mice developed age-related OA but with a high degree of variability and without a significant effect of the tested ITP treatments. High variability was also seen in the Ames dwarf mice but differences in several measures suggested some protection from OA.
Bibliographical noteFunding Information:
This study was supported by grants from the National Institute on Aging (RO1 AG044034 and U01 AG022303) as well as the Glenn Medical Foundation. The authors would like to thank Dr. Andrzej Bartke from Southern Illinois University for mouse hindlimbs from Ames dwarf and age-matched control mice.