Sphingosine-1-phosphate promotes osteogenesis by stimulating osteoblast growth and neovascularization in a vascular endothelial growth factor-dependent manner.

Autor:	Wille A; Institute of Molecular Medicine III, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Weske S; Institute of Molecular Medicine III, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., von Wnuck Lipinski K; Institute of Molecular Medicine III, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Wollnitzke P; Institute of Molecular Medicine III, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Schröder NH; Institute of Molecular Medicine III, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Thomas N; Institute of Molecular Medicine III, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Nowak MK; Institute of Molecular Medicine III, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Deister-Jonas J; Institute of Molecular Medicine III, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Behr B; Department of Plastic Surgery, University Hospital BG Bergmannsheil, 44789 Bochum, Germany., Keul P; Institute of Molecular Medicine III, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Levkau B; Institute of Molecular Medicine III, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
Jazyk:	angličtina
Zdroj:	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2024 Apr 19; Vol. 39 (3), pp. 357-372.
DOI:	10.1093/jbmr/zjae006
Abstrakt:	Sphingosine-1-phosphate (S1P) plays multiple roles in bone metabolism and regeneration. Here, we have identified a novel S1P-regulated osteoanabolic mechanism functionally connecting osteoblasts (OBs) to the highly specialized bone vasculature. We demonstrate that S1P/S1PR3 signaling in OBs stimulates vascular endothelial growth factor a (VEGFa) expression and secretion to promote bone growth in an autocrine and boost osteogenic H-type differentiation of bone marrow endothelial cells in a paracrine manner. VEGFa-neutralizing antibodies and VEGF receptor inhibition by axitinib abrogated OB growth in vitro and bone formation in male C57BL/6J in vivo following S1P stimulation and S1P lyase inhibition, respectively. Pharmacological S1PR3 inhibition and genetic S1PR3 deficiency suppressed VEGFa production, OB growth in vitro, and inhibited H-type angiogenesis and bone growth in male mice in vivo. Together with previous work on the osteoanabolic functions of S1PR2 and S1PR3, our data suggest that S1P-dependent bone regeneration employs several nonredundant positive feedback loops between OBs and the bone vasculature. The identification of this yet unappreciated aspect of osteoanabolic S1P signaling may have implications for regular bone homeostasis as well as diseases where the bone microvasculature is affected such as age-related osteopenia and posttraumatic bone regeneration. (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)
Databáze:	MEDLINE
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