The effect of microgravity on osteoblast metabolism

摘要

Several reports have shown the deleterious effects of weightlessness on astronauts. Among the pathological conditions recorded, those involving the skeleton are dramatic, characterised by a decrease of bone mass and by bone demineralization, eventually leading to osteoporosis. This is consistent with the notion that mechanical loading is critical for the maintenance of a correct bone mass, since it has an anabolic effect by activating bone formation and inhibiting bone resorption. Space flight experiments, as well as ground-based studies performed using different models of simulated microgravity, demonstrated that bone loss could, at least in part, be due to a decrease in bone formation by osteoblasts, the cells of the bone tissue devoted to build the bone matrix. Interestingly, it seems that osteoblasts themselves are directly sensitive to the reduced gravity force, which in turn acts by impairing their differentiation and function, as demonstrated by a decrease of the expression of the osteoblast master gene runx2 and of the specific osteoblast marker ALP, along with a decrease of the production of the bone matrix proteins osteocalcin, collagen 1 alpha 1 and osteopontin. Consistently, weightlessness also induced a reduction of osteoblast life-span and an increase of apoptosis. Based on this evidence, there is the need to more deeply investigate the molecular mechanisms underlying weightlessness-induced bone loss, in order to identify new molecular targets for alternative therapies, useful to counteract the deleterious effects of weightlessness in astronauts as well as to cure pathological conditions of reduced bone mass on earth.del