Erythropoietin signaling in osteoblasts is required for normal bone formation and for bone loss during erythropoietin-stimulated erythropoiesis

Sukanya Suresh, Jeeyoung Lee, Constance T. Noguchi

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Erythropoietin (EPO) regulates erythropoiesis by binding to erythropoietin receptor (Epor) on erythroid progenitor cells. Epor is also expressed on bone forming osteoblasts and bone loss accompanies EPO-stimulated erythropoiesis in mice. Mice with Epor restricted to erythroid tissue exhibit reduced bone and increased marrow adipocytes; in contrast, transgenic mice (Tg) with osteoblastic-specific deletion of Epor exhibit reduced trabecular bone with age without change in marrow adipocytes. By 12 weeks, male Tg mice had 22.2% and female Tg mice had 29.6% reduced trabecular bone volume (BV) compared to controls. EPO administration (1200 U/kg) for 10 days reduced trabecular bone in control mice but not in Tg mice. There were no differences in numbers of osteoblasts, osteoclasts, and marrow adipocytes in Tg mice, suggesting independence of EPO signaling in mature osteoblasts, osteoclasts, and adipocytes. Female Tg mice had increased number of dying osteocytes and male Tg mice had a trend for more empty lacunae. Osteogenic cultures from Tg mice had reduced differentiation and mineralization with reduced Alpl and Runx2 transcripts. In conclusion, endogenous EPO-Epor signaling in osteoblasts is important in bone remodeling, particularly trabecular bone and endogenous Epor expression in osteoblasts is required for bone loss accompanying EPO-stimulated erythropoiesis.

Original languageEnglish (US)
Pages (from-to)11685-11697
Number of pages13
JournalFASEB Journal
Volume34
Issue number9
DOIs
StatePublished - Sep 1 2020
Externally publishedYes

Keywords

  • EPO
  • bone remodeling
  • osteoblast differentiation
  • osteocyte
  • trabecular

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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