Possible Role of Deferoxamine in Autophagy Regulation Via Divalent Metal Transporter-1 (DMT1) in a Rat Model of Liver Cirrhosis-Induced Osteoporosis

Abstract

Cirrhosis is the leading cause of liver-related death globally which is the end-stage of CLD regardless the etiology. Almost all patients with CLD show altered bone metabolism. Many risk factors share in the pathogenic mechanisms of osteoporosis in CLD with iron overload being a major cause of osteoporosis through inhibition of osteoblast function, in addition to promotion of osteoclastogenesis.

DMT1 is the primary importer of non-heme iron and is highly expressed in proximal duodenum (iron uptake) and liver (iron storage). Moreover, DMT1 was found to be expressed in various other tissues, such as bone and kidney. It was found that DMT1 is markedly increased in osteoporosis, and that loss of DMT1 can lead to loss of iron content in bone. Some studies suggested a link between DMT1 expression and autophagic activity in bone.

Autophagy is a lysosomal degradation pathway responsible for degradation and recycling of cellular components such as unnecessary organelles and proteins, and also serves to destroy intracellular pathogens, in addition to playing an important role in maintenance of bone homeostasis. Several studies have shown that iron overload was found to promote cell autophagy, which in turn can promote the development of hepatic fibrosis through activation of hepatic stellate cells.