60 days aboard the ISS damaged mouse knee cartilage, and researchers linked the damage to mitochondrial dysfunction
60 days aboard the ISS damaged mouse knee cartilage, and researchers linked the damage to mitochondrial dysfunction
In a paper published on July 9, mice that spent 60 days aboard the International Space Station and mice exposed to a ground-based flight model lost part of the cartilage matrix in their knees. In a human cartilage model, microgravity reduced cellular energy production and increased oxidative stress. The authors identified the enzyme NOX4 as a likely component of this pathway.
Space medicine has long regarded bone loss and muscle atrophy as major risks. Articular cartilage has received less attention, although it distributes loads across the knee and has little capacity for repair. A team from the University of Pittsburgh compared six mice that had spent 60 days aboard the ISS with six ground controls. A second group of mice underwent a ground-based simulation of spaceflight that combined hindlimb unloading with a radiation dose approximating galactic radiation. In both models, the cartilage lost glycosaminoglycans, which are water-retaining matrix molecules, and collagen II. Histological damage scores increased.
To investigate how the damage occurred, the researchers grew cartilage from human cells in a hydrogel and rotated it in a device that simulates microgravity. After 14 days, the cells showed impaired respiration: oxygen consumption, АТФ production, and spare energy capacity all decreased. At the same time, reactive oxygen species, inflammatory signals, and p21 increased. p21 is a protein often associated with cellular senescence. The cells also produced more MMP-13, an enzyme that breaks down cartilage collagen.
NOX4 emerged as a possible regulator of this cascade. This enzyme produces reactive oxygen species. Its level increased under simulated microgravity, while suppressing NOX4 in the cells reduced inflammation and restored features of healthy cartilage. The authors confirmed that kaempferol, a plant flavonoid, binds to NOX4. They also found that excess NOX4 reversed part of the molecule's protective effect. The study therefore goes beyond the general claim that oxidative stress is high in space. It tests a specific point in the pathway through which that stress may damage tissue.
The mice in the ground-based model received oral kaempferol. They retained more cartilage matrix and collagen II, and their NOX4 levels decreased. This result comes from a short experiment in mice: kaempferol has not yet been tested during actual spaceflight. The authors also do not yet know whether such an early signal will lead to osteoarthritis in humans.
NOX4 already has a history in osteoarthritis research. Knocking it out protected mouse cartilage in ground-based disease models. The new paper extends that evidence to spaceflight conditions. Long missions will require the preservation of muscle, bone, and articular cartilage. The effects on cartilage still need to be studied separately in humans and during actual spaceflight.