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PTH regulates myleoid ELF‐1‐like factor (MEF)‐induced MAB‐21‐like‐1 (MAB21L1) expression through the JNK1 pathway
Author(s) -
Kim ByungGyu,
Park YounJe,
Libermann Towia A.,
Cho JeYoel
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23124
Subject(s) - microbiology and biotechnology , chemistry , expression (computer science) , biology , computer science , programming language
Continuous treatment with parathyroid hormone (PTH) or excess endogenous PTH due to primary hyperparathyroidism causes increased bone resorption and, subsequently, decreased bone volume. Our previous studies showed that myeloid Elf‐1‐like factor (MEF) not only suppresses osteoblast differentiation through inhibition of Runx2 activity and other osteogenesis‐related genes but also specifically increases the expression of Mab21, a potential transcriptional repressor of osteoblast differentiation. Here we show that the JNK1 pathway is involved in the MEF‐mediated up‐regulation of Mab21 expression due to PTH stimulation. PTH increased the transcription level of Mab21 in MG63 human osteoblastic cells, in contrast to the suppressive effect of TGFβ1. PTH phosphorylates serine residues of MEF as well as c‐Jun, a known substrate of JNK1. By in vitro kinase assay, we confirmed that MEF is phosphorylated by JNK1, but not by ERK. Co‐transfection of MEF with both MKK4 and JNK1 increased the promoter activity of Mab21 in CV1 cells significantly more than MEF alone. We also identified the phosphorylation of MEF serine 641 by in vitro and in vivo JNK1 kinase assays combined with a proteomics approach. In conclusion, our findings indicate that MEF is involved in PTH suppression of osteoblasts through activating the MKK4/JNK1 pathway and subsequently up‐regulating Mab21 expression. J. Cell. Biochem. 112: 2051–2061, 2011. © 2011 Wiley‐Liss, Inc.