Expression of nephronectin is inhibited by oncostatin M via both JAK/STAT and MAPK pathways

Tamaki Kurosawa; Atsushi Yamada; Masamichi Takami; Dai Suzuki; Yoshiro Saito; Katsuhiro Hiranuma; Takuya Enomoto; Naoko Morimura; Matsuo Yamamoto; Takehiko Iijima; Tatsuo Shirota; Hiroyuki Itabe; Ryutaro Kamijo

doi:10.1016/j.fob.2015.04.001

Expression of nephronectin is inhibited by oncostatin M via both JAK/STAT and MAPK pathways

FEBS Open Bio. 2015 Apr 8:5:303-7. doi: 10.1016/j.fob.2015.04.001. eCollection 2015.

Authors

Affiliations

¹ Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan ; Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, Shinagawa, Tokyo 142-8555, Japan.
² Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.
³ Department of Pharmacology, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan.
⁴ Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan ; Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan.
⁵ Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan ; Department of Perioperative Medicine Division of Anesthesiology, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan.
⁶ Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan ; Department of Periodontology, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan.
⁷ Brain Science Laboratory, The Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
⁸ Department of Periodontology, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan.
⁹ Department of Perioperative Medicine Division of Anesthesiology, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan.
¹⁰ Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan.
¹¹ Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, Shinagawa, Tokyo 142-8555, Japan.

Abstract

Nephronectin (Npnt), also called POEM, is an extracellular matrix protein considered to play critical roles as an adhesion molecule in the development and functions of various tissues, such as the kidneys, liver, and bones. In the present study, we examined the molecular mechanism of Npnt gene expression and found that oncostatin M (OSM) strongly inhibited Npnt mRNA expression in MC3T3-E1 cells from a mouse osteoblastic cell line. OSM also induced a decrease in Npnt expression in both time- and dose-dependent manners via both the JAK/STAT and MAPK pathways. In addition, OSM-induced inhibition of osteoblast differentiation was recovered by over-expression of Npnt. These results suggest that OSM inhibits Npnt expression via the JAK/STAT and MAPK pathways, while down-regulation of Npnt by OSM influences inhibition of osteoblast differentiation.

Keywords: BMP-2, bone morphogenetic protein-2; ERK, extracellular signal-regulated kinase; JAK, janus kinase; JAK/STAT; JNK, c-Jun N-terminal kinase; MAM, meprin, A5 protein, and receptor protein-tyrosine phosphatase μ; MAPK; MAPK, mitogen-activated protein kinase; MEF2, myocyte enhancer-binding factor 2A; Nephronectin; Npnt, nephronectin; OSM, oncostatin M; OSMR, OSM receptor; Oncostatin M; STAT, signal transducer and activator of transcription; TGF-β, transforming growth factor-β; TNF-α, tumor necrosis factor-α.