Sclerostin stimulates angiogenesis in human endothelial cells

Angela Oranger, Giacomina Brunetti, Graziana Colaianni, Roberto Tamma, Claudia Carbone, Luciana Lippo, Giorgio Mori, Paolo Pignataro, Nunzio Cirulli, Roberta Zerlotin, Biagio Moretti, Angela Notarnicola, Domenico Ribatti, Maria Grano, Silvia Colucci

Research output: Contribution to journalArticle

Abstract

Sclerostin, negative regulator of bone formation, has been originally known as an osteocyte product. Recently, it has been also detected in hypertrophic chondrocytes, distinctive cells of avascular cartilage which is invaded by capillaries and then replaced by vascularized bone. Thus, we hypothesized that sclerostin, in addition to its role already known, may exert an angiogenic activity. We first proved that sclerostin increased the proliferation of human umbilical vein endothelial cells (HUVECs), and next, by using the chicken chorioallantoic membrane (CAM) in vivo assay, we demonstrated that it exerts an angiogenic activity similar to that of vascular endothelial growth factor (VEGF). This last finding was reinforced by several in vitro approaches. Indeed, we showed that sclerostin induced the formation of a network of anastomosing tubules, a significant increase in the percentage of tubule number, total tubule length and number of junctions, as well as the ability of sclerostin-stimulated HUVECs to organize capillary-like structures and closed-meshes similar to VEGF. The angiogenic response elicited by the protein may be due to the binding to its receptor, LRP6, which is highly expressed at mRNA and protein levels by sclerostin treated HUVECs and through the production of two well-known pro-angiogenic cytokines, VEGF and placental growth factor (PlGF). Finally, we demonstrated that sclerostin was also responsible for the recruitment of osteoclasts and their circulating monocyte progenitors. Overall, these findings showed for the first time the new angiogenic in vitro role of sclerostin which could be also considered as a novel molecule in angiogenesis-osteogenesis coupling.

Original languageEnglish
Pages (from-to)26-36
Number of pages11
JournalBone
Volume101
DOIs
Publication statusPublished - Aug 1 2017

Keywords

  • Angiogenesis
  • Bone formation
  • Endothelial cells
  • Sclerostin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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  • Cite this

    Oranger, A., Brunetti, G., Colaianni, G., Tamma, R., Carbone, C., Lippo, L., Mori, G., Pignataro, P., Cirulli, N., Zerlotin, R., Moretti, B., Notarnicola, A., Ribatti, D., Grano, M., & Colucci, S. (2017). Sclerostin stimulates angiogenesis in human endothelial cells. Bone, 101, 26-36. https://doi.org/10.1016/j.bone.2017.03.001