Oxidative stress reaction in the meniscus of Bach 1 deficient mice: potential prevention of meniscal degeneration.

Bach 1 is a transcription factor that negatively regulates the transcription of heme oxygenase-1 (HO-1), a stress-responding protein. In this study, we investigated the reaction to oxidative stress in the meniscus of Bach 1 deficient mice, and the suppression of meniscal degeneration by the induction of HO-1. We carried out a comparative study between Bach 1 deficient mice and wild type mice, in which the oxidative stress reaction and age-related changes were investigated using the menisci of 6-, 12-, and 24-week-old mice. The degrees of meniscal degeneration and expression of HO-1 were evaluated using the menisci cultured under oxidative stress with cadmium chloride or interleukin-1 beta. The age-related changes in the meniscus were histologically examined. The expression of HO-1 was higher, and the degrees of histological degeneration were lower in the Bach 1 deficient mice than in wild type mice (HO-1 mRNA expression: In both the Cd group and the IL group, two-fourfold higher in the meniscus). The age-related changes were lower in the Bach 1 deficient mice than in wild type mice. In 24-week-old mice, a moderate decrease in the cell density and proteoglycan content was observed in wild type mice compared with Bach 1 deficient mice. In the menisci of Bach 1 deficient mice, the anti-oxidative stress activity was considered to be increased by abrogating the suppression of HO-1 expression, resulting in a reduction of histological degeneration. This finding showed a potential new strategy for the prevention and treatment of meniscal degeneration. (c) 2008 Orthopaedic Research Society.