Iron Accumulation Leads to Bone Loss by Inducing Mesenchymal Stem Cell Apoptosis Through the Activation of Caspase3

Abstract

Osteoporosis (OP) is a disease associated with bone loss and microstructure degradation. Recent studies have shown that iron accumulation may be a risk factor for OP. Bone marrow mesenchymal stem cells (MSCs) are multipotent cells and precursors to osteoblasts. MSCs play an important role in OP. Therefore, we evaluated the correlation between MSCs and OP in an environment of iron accumulation. Serum P1NP was decreased in iron accumulation mice. Micro-CT revealed that iron accumulation decreased bone mineral density and spatial structural parameters. Iron accumulation inhibited MSC quantity in bone marrow. However, the iron chelator deferoxamine (DFO) rescued the suppression. Iron accumulation also changed the MSC cell cycle. Iron elevated MSC cell ROS level and NOX4 protein expression. MSC apoptosis was increased, and more caspase3 was cleaved after iron intervention. Our data suggests that iron accumulation inhibits MSC quantity and induces MSC apoptosis. Bone loss from iron accumulation may correlate with the inhibition of MSCs.

Keywords: Bone loss; Bone marrow mesenchymal stem cells; Iron accumulation.