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CTGF/CCN2 induction by TGF‐1 β requires Ets‐1 in osteoblasts
Author(s) -
Arnott John,
Geisinger Max,
Astaiza Randy,
Butler Tiffany,
Popoff Steven,
Planey Sonia
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.929.4
Subject(s) - ctgf , growth factor , transcription factor , transforming growth factor , microbiology and biotechnology , osteoblast , smad , biology , chemistry , cancer research , genetics , gene , in vitro , receptor
Erythroblastosis virus E26 oncogene homologue 1 (Ets‐1) is the founding member of the Ets family of transcription factors that control cell proliferation, differentiation and ECM regulation. Ets‐1 participates in osteoblast differentiation; however, its mechanism of action remains largely undetermined. CTGF acts as an anabolic growth factor to regulate osteoblast differentiation and function. CTGF is induced by TGF‐β1 and mediates TGF‐β1 induced matrix production in osteoblasts, but the mechanisms that control CTGF induction by TGF‐β1 are not understood. This study investigates the role of Ets‐1 in CTGF induction by TGF‐β1 in osteoblasts. We demonstrate that: Ets‐1 expression is induced by TGF‐β1 treatment, that overexpression of Ets‐1 induces CTGF protein, and promoter activity similar to TGF‐β1 treatment alone and that Ets‐1 expression synergizes with TGF‐β1 to induce CTGF promoter activation and that Ets‐1 siRNA impaires CTGF expression. Bioinformatic analysis identified eight putative Ets‐1 binding motifs in the CTGF promoter. Using site‐directed mutagenesis, we found that mutation of EBE sites, especially in close proximity to the Smad binding element (SBE), had a more severe impact on CTGF expression suggesting that the Ets‐1 sites may cooperate with Smads to achieve CTGF expression following TGF‐β1 treatment in osteoblasts. This study was funded by NIAMS.