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Platelet-Derived Growth Factor Stimulates Osteoprotegerin Production in Osteoblastic Cells

Abstract

Osteoprotegerin (OPG) is a major regulator of osteoclastogenesis, bone resorption and vascular calcification. OPG is produced by various cell types including mesenchymally derived cells, in particular, osteoblastic cells. Here we show OPG production by osteoblastic cells was stimulated by platelet-derived growth factor (PDGF) in two human osteosarcoma cell lines (MG63, Saos-2), a mouse pre-osteoblastic cell line (MC3T3-E1) and human bone marrow stromal cells (hMSC) by 152%, 197%, 113% and 45% respectively over 24 h. OPG was measured in the cell culture medium by immunoassay. PDGF isoforms AA, BB and AB show similar stimulation of OPG production. Message for OPG was also increased similarly to the increased secretion into the culture medium. Using specific inhibitors of cell signalling we demonstrate that PDGF acts through the PDGF receptor, PKC, PI3K, ERK and P38 and not via NF-kB or JNK. The importance of PDGF in fracture healing suggests a role for OPG production in countering bone resorption during the early phase of this process.

Acceptance Date Aug 27, 2008
Publication Date Sep 22, 2008
Journal Journal of Cellular Physiology
Print ISSN 0021-9541
Publisher Wiley
Pages 350-354
DOI https://doi.org/10.1002/jcp.21600
Publisher URL https://doi.org/10.1002/jcp.21600

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