Treatment with a superoxide dismutase mimetic for joint preservation during 35 and 75 days in orbit aboard the international space station, and after 120 days recovery on Earth

Abstract

Reduced weight-bearing during spaceflight has been associated with musculoskeletal degradation that risks astronaut health and performance in transit and upon reaching deep space destinations. Previous rodent experiments aboard the international space station (ISS) have identified that the spaceflight-induced molecular arthritic phenotype was characterized with an increase in oxidative stress. This study evaluated if treatment with a superoxide dismutase (SOD) mimetic on orbit could prevent spaceflight-induced damage to the knee and hip articular cartilage, and the menisci in rodents. Cartilage and meniscal degradation in mice were measured via microCT, histology, and transcriptomics after: (1) ∼ 35 days on the ISS, (2) ∼ 35 days on the ISS followed by 120 days weight-bearing readaptation on Earth or (3) ∼ 75 days on the ISS. The study had a limited sample size, so both significant effects and generalized patterns are reported. After 35 days aboard the ISS, cartilage volume at the tibial-femoral cartilage-cartilage contact point decreased, meniscal volume decreased concurrent with an increase in pro-osteoarthritic signaling in the joint soft tissue. Similarly, a decrease in cortical and trabecular bone volume of the tibia was observed. Treatment with the SOD mimetic preserved the trabecular bone, articular cartilage and the menisci after 35 days aboard the ISS, but had limited efficacy retaining that recovery after 120 days of weight bearing, and after 75 days on orbit. Antioxidants including BuOE may serve as a potential countermeasure option to protect musculoskeletal health during spaceflight missions, and continued use may be necessary upon reaching a destination.