Regulation of human bone marrow stromal cell proliferation and differentiation capacity by glucocorticoid receptor and AP-1 crosstalk

Iván Cárcamo-Orive, Ainhoa Gaztelumendi, Jesús Delgado, Naiara Tejados, Akaitz Dorronsoro, Jon Fernández-Rueda, Daniel J. Pennington, César Trigueros

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Although marrow adipocytes and osteoblasts derive from a common bone marrow stromal cells (BMSCs), the mechanisms that underlie osteoporosis-associated bone loss and marrow adipogenesis during prolonged steroid treatment are unclear. We show in human BMSCs (hBMSCs) that glucocorticoid receptor (GR) signaling in response to high concentrations of glucocorticoid (GC) supports adipogenesis but inhibits osteogenesis by reducing c-Jun expression and hBMSC proliferation. Conversely, significantly lower concentrations of GC, which permit hBMSC proliferation, are necessary for normal bone mineralization. In contrast, platelet-derived growth factor (PDGF) signaling increases both JNK/c-Jun activity and hBMSC expansion, favoring osteogenic differentiation instead of adipogenesis. Indeed, PDGF antagonizes the proadipogenic qualities of GC/GR signaling. Thus our results reveal a novel c-Jun-centered regulatory network of signaling pathways in differentiating hBMSCs that controls the proliferation-dependent balance between osteogenesis and adipogenesis.

Original languageEnglish (US)
Pages (from-to)2115-2125
Number of pages11
JournalJournal of Bone and Mineral Research
Volume25
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • Adipose
  • Bone
  • Corticosteroid osteoporosis
  • Osteoblasts and stem cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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    Cárcamo-Orive, I., Gaztelumendi, A., Delgado, J., Tejados, N., Dorronsoro, A., Fernández-Rueda, J., Pennington, D. J., & Trigueros, C. (2010). Regulation of human bone marrow stromal cell proliferation and differentiation capacity by glucocorticoid receptor and AP-1 crosstalk. Journal of Bone and Mineral Research, 25(10), 2115-2125. https://doi.org/10.1002/jbmr.120