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.
Ochiai
Satoshi
S
Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, 734-8551 Japan.
Mizuno
Toshiyuki
T
Deie
Masataka
M
Igarashi
Kazuhiko
K
Hamada
Yoshiki
Y
Ochi
Mitsuo
M
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D019256:Cadmium Chloride / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D008592:Menisci, Tibial / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism
C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D053583:Interleukin-1beta; D011509:Proteoglycans; D051547:Heme Oxygenase-1; D019256:Cadmium Chloride