| The following article features coverage from the 61st American Society of Hematology Annual Meeting and Exposition. Click here to read more of Hematology Advisor’s conference coverage. |
The bone marrow-secreted protein erythroferrone (ERFE) may play an integral role in the coordination of iron metabolism, erythropoiesis, and bone hemostasis, according to research presented at the 61st American Society of Hematology (ASH) Annual Meeting in Orlando, Florida.
ERFE negatively regulates hepcidin by sequestering bone morphogenetic proteins (BMPs), thereby increasing the availability of iron during stress erythropoiesis. Because BMPs are also involved in bone metabolism, and because diseases such as beta thalassemia that involve ineffective erythropoiesis are associated with increased levels of ERFE, researchers hypothesized that ERFE expression may play a role in coordinating iron metabolism, erythropoiesis, and bone remodeling.
Thalassemic (th3/+) mice with ERFE loss (ERFE-/-) exhibited decreased bone mineral density (whole body, P <.05) and ratio of bone volume to total volume, as well as increased femoral mineral apposition rate, compared with th3/+ mice. Osteoclast activity was also increased in ERFE-/- and th3/+ ERFE-/- mice compared with wild type and th3/+ mice, respectively. These findings were unexpected, as the researchers had predicted that ERFE negatively regulates osteoblast activity and therefore, th3/+ ERFE-/- mice would exhibit increased bone mineral density. Instead, these results indicate that osteoblast activity was enhanced, though bone formation was not, when ERFE was knocked out.
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The researchers found that ERFE was secreted by osteoblasts and osteoclasts collected from wild type mice, leading to suppression of hepcidin, and that BMPs 2, 6, and 7 enhanced ERFE expression. ERFE loss in osteoblasts was associated with promotion of bone resorption through stimulation of sclerostin, with ERFE-/- mice exhibiting enhanced bone mineralization and increased expression of both osteoblast-specific markers and sclerostin compared with wild type mice (P <.001 for both).
The researchers also analyzed the role of TfR2 in bone metabolism, as previous research has shown that TfR2 inhibits bone formation by enhancing sclerostin expression. ERFE-/- osteoblasts exhibited a trend toward decreased TfR2, which is consistent with the hypothesis that TfR2 plays an important role in bone metabolism.
“ERFE loss in beta thalassemia has an effect on both bone formation and resorption, with a larger effect on formation,” noted presenter Melanie Castro-Mollo, MS, of the Icahn School of Medicine at Mount Sinai in New York, New York. “ERFE is an important protective mechanism to prevent excessive bone loss in beta thalassemia.”
Reference
1. Castro-Mollo M, Martinez MR, Feola M, et al. Erythroferrone regulates bone remodeling in β-thalassemia. Oral presentation at: 61st ASH Annual Meeting and Exposition; December 7-10; Orlando, FL. Abstract 2.
