Antioxidant treatment with vitamin C attenuated rotator cuff degeneration caused by oxidative stress in Sod1-deficient mice

BACKGROUND: Rotator cuff degeneration is 1 of several factors that lead to rotator cuff tears; however, the mechanism of this degeneration remains unclear. We previously reported that deficiency of an antioxidant enzyme, superoxide dismutase 1 (Sod1), in mice induced degeneration in supraspinatus tendon entheses, a model that replicates human rotator cuff degeneration. In this study, we analyzed possible effects of vitamin C (VC), a major antioxidant, on the degenerative changes of supraspinatus entheses in Sod1(−/−) mice. METHODS: We administered VC or vehicle, distilled water, for 8 weeks to Sod1(−/−) and wild-type male mice beginning at 12 weeks of age (n = 5-8 per group). When mice were 20 weeks of age, we sectioned rotator cuff tissue samples and performed hematoxylin-eosin and toluidine blue staining for quantitative histologic evaluation. RESULTS: VC administration, compared with vehicle administration, attenuated the histologic changes, including a misaligned 4-layered structure, fragmented tidemark, and toluidine blue staining, in the supraspinatus entheses of Sod1(−/−) mice. In the quantitative histologic evaluation, all parameters were significantly decreased in Sod1(−/−) mice compared with wild-type mice, except for the number of nonchondrocytes. CONCLUSION: We demonstrated that an antioxidant treatment, VC administration, attenuated the rotator cuff degeneration, similar to that observed in humans, that is caused by oxidative stress in Sod1(−/−) mice. VC effects included improvements in quantitative histologic parameters and other histologic changes. These results suggest that VC treatment can prevent oxidative stress–induced degeneration of the rotator cuff.