Iron overload inhibits osteogenesis and promotes adipogenesis in human bone marrow mesenchymal stem cells by producing reactive oxygen / 中国组织工程研究

ABSTRACT

BACKGROUND:Iron overload as a new etiological factor participate in the pathogenesis of senile osteoporosis, but its mechanism remains unclear. But the mechanism of iron overload cause senile osteoporosis pathogenesis remains unclear. Osteogenic/adipogenic differentiation homeostasis of bone marrow mesenchymal stem cel s (BMSCs) plays an important role in the maintenance of normal human bone mass, and its imbalance can lead to senile osteoporosis. Iron effects on the osteogenic/adipogenic differentiation of BMSCs remain unclear. Therefore, we clarify the role of iron overload in the pathogenesis of senile osteoporosis by studying the effect of iron overload on BMSCs osteogenic/adipogenic differentiation. OBJECTIVE:To explore the effect of iron overload on the osteogenesis and adipogenesis of human BMSCs (hBMSCs) in vitro and to explicit the role of iron overload in the pathogenesis of senile osteoporosis. METHODS:hBMSCs were isolated by using density gradient centrifugation method. Isolated cel s were treated with normal saline as normal control group, treated with 10, 20, 30μmol/L ferrous citrate to mimic iron overload conditions, or treated with 30μmol/L ferrous citrate fol owed by 0.5 mmol/L N-acetylcysteine as an antioxidant. RESULTS AND CONCLUSION:Iron overload did not remarkably inhibit the proliferation of hBMSCs, but it could promote the generation of reactive oxygen in hBMSCs. After treatment with ferrous citrate, the expression of c-Maf and Runx2 decreased, and the expression of peroxisome proliferator-activated receptorγincreased;moreover, formation of calcium nodules decreased, but lipid droplets were produced. N-acetylcysteine could inhibit the production of reactive oxygen and increase the expression of c-Maf induced by iron overload. These findings indicate that iron overload inhibits osteogenesis and promotes adipogenesis in hBMSCs through the generation of reactive oxygen. Meanwhile, c-Maf plays an essential role in the iron-overload induced differetiation imbalance.