title: Oncostatin M regulates osteogenic differentiation of murine adipose-derived mesenchymal progenitor cells through a PKCdelta-dependent mechanism.
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.
authors: Currently at University of Ottawa Heart Institute, University of Ottawa, Ottawa, ON, Canada.
authors: David C
authors: DC
authors: Smyth
authors: Shunsuke
authors: S
authors: Takenaka
authors: Celine
authors: C
authors: Yeung
authors: Carl D
authors: CD
authors: Richards
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D053683:Oncostatin M / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*; D051745:Protein Kinase C-delta / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; D053683:Oncostatin M; C497259:Prkcd protein, mouse; D051745:Protein Kinase C-delta