Abstract
Oncostatin M (OSM) is an IL-6/LIF family cytokine that influences mesenchymal progenitor differentiation; however, the mechanisms of this activity have not been fully elucidated. Using uncommitted murine adipose tissue-derived mesenchymal progenitors, we have examined mechanisms of OSM-induced osteogenesis. Murine OSM (mOSM) induced osteogenic differentiation to a greater degree than interleukin (IL)-6 and other members of the gp130 cytokine family, promoting extracellular matrix mineralization as indicated by Alizarin Red S staining. mOSM also increased expression of osteogenesis-associated gene products BMP4, BMP7, Runx-2, and osteocalcin as assessed by immunoblotting and real-time quantitative PCR. Additionally, protein kinase C (PKC) delta activity was upregulated in response to OSM stimulation, and to a greater degree than IL-6. Knockdown of PKCdelta expression by use of RNA interference (RNAi) reduced OSM-mediated osteogenic differentiation and decreased expression of Runx-2. These findings suggest that OSM differentially promotes osteogenesis in non-committed mesenchymal progenitors relative to other gp130 cytokines. This activity correlates with selective activation of PKCdelta in OSM-treated cells, indicating that OSM-induced osteogenesis and upregulation of osteogenic gene products require activity of PKCdelta.
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Acknowledgments
The authors want to thank Christine Demers, Carrie M. Langdon, and Rebecca Rodrigues (McMaster University) for excellent technical assistance, and Steven Wong (McMaster University) for review of the manuscript. This work was supported by CIHR grant # 102565.
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Smyth, D.C., Takenaka, S., Yeung, C. et al. Oncostatin M regulates osteogenic differentiation of murine adipose-derived mesenchymal progenitor cells through a PKCdelta-dependent mechanism. Cell Tissue Res 360, 309–319 (2015). https://doi.org/10.1007/s00441-014-2099-y
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DOI: https://doi.org/10.1007/s00441-014-2099-y