Osteopontin regulates actin cytoskeleton and contributes to cell proliferation in primary erythroblasts

Jeong Ah Kang, Ying Zhou, Tahlia L. Weis, Hui Liu, Jodie Ulaszek, Nilesh Satgurunathan, Li Zhou, Koen Van Besien, John Crispino, Amit Verma, Philip S. Low, Amittha Wickrema

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31 Scopus citations

Abstract

Erythropoietin and stem cell factor are the key cytokines that regulate early stages of erythroid differentiation. However, it remains undetermined whether additional cytokines also play a role in the differentiation program. Here, we report that osteopontin (OPN) is highly expressed and secreted by erythroblasts during differentiation. We also demonstrate that OPN-deficient human and mouse erythroblasts exhibit defects in F-actin filaments, and addition of exogenous OPN to OPN-deficient erythroblasts restored the F-actin filaments in these cells. Furthermore, our studies demonstrate that OPN contributes to erythroblast proliferation. OPN knock-out male mice exhibit lower hematocrit and hemoglobin levels compared with their wild-type counterparts. We also show that OPN mediates phosphorylation or activation of multiple proteins including Rac-1 GTPase and the actin-binding protein, adducin, in human erythroblasts. In addition, we show that theOPNeffects include regulation of intracellular calcium in human erythroblasts. Finally, we demonstrate that human erythroblasts express CD44 and integrins β1 and α4, three known receptors for OPN, and that the integrin β1 receptor is involved in transmitting the proliferative signal. Together these results provide evidence for signal transduction by OPN and contribution to multiple functions during the erythroid differentiation program in human and mouse.

Original languageEnglish (US)
Pages (from-to)6997-7006
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number11
DOIs
StatePublished - Mar 14 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kang, J. A., Zhou, Y., Weis, T. L., Liu, H., Ulaszek, J., Satgurunathan, N., Zhou, L., Van Besien, K., Crispino, J., Verma, A., Low, P. S., & Wickrema, A. (2008). Osteopontin regulates actin cytoskeleton and contributes to cell proliferation in primary erythroblasts. Journal of Biological Chemistry, 283(11), 6997-7006. https://doi.org/10.1074/jbc.M706712200