Highlights from

ASH 2019

61st Annual Meeting & Exposition of the American Society of Hematology

Orlando, Florida (USA) 7 - 10 December 2019

Erythroferrone and skeletal changes associated with thalassaemia

Dr Melanie Castro-Mollo (Icahn School of Medicine at Mount Sinai, USA) presented her team’s research into the molecular mechanism for the skeletal changes associated with thalassaemia [1].

Patients with β-thalassaemia are known to have low bone mass due to decreased mineral density and cortical thinning, but the role of erythroferrone (ERFE) in causing these changes was unknown. ERFE suppresses hepcidin via the sequestration of bone morphogenetic proteins (BMPs)—positive regulators of hepcidin via its interaction with haemojuvelin. ERFE is produced by erythroblasts, thereby increasing iron availability for haematopoiesis as the inhibition by hepcidin on iron absorption is removed. Dr Castro-Mollo described how BMPs are also produced by osteoblasts to varying degrees throughout their maturation process, at even higher levels than those produced by erythroblasts. This discovery led to the hypothesis that ERFE regulates bone formation and remodelling.

To explore their hypothesis, Dr Castro-Mollo used ERFE knockout mice, both with and without thalassaemia. Surprisingly these mice were found to have low bone mass. This result was unexpected, as the thought was that by losing ERFE there would be no sequestration of BMPs, and as a result, a higher bone mass was expected. The researchers confirmed that ERFE loss did result in decreased BMP, but its loss in osteoblasts increased production of sclerostin, which has a role in increasing osteoclastogenesis via RANKL upregulation. The increased density of osteoclasts appeared to be the explanation for the decreased bone mineral density, as cortical sampling from ERFE–/– mice did reveal an increased density of osteoclasts.

The exact mechanism behind this process is still under investigation, but Dr Castro-Mollo suspects it could be that only certain types of BMPs are directly affected by changes in ERFE, altering the overall BMP signalling environment and thus the activity of osteoblasts and osteoclasts.

Keywords: Thalassaemia; Anaemia; erythroferrone; Bone Morphogenetic Proteins

Top image: @ iStockPhoto: ustas7777777

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