Oxidative stress‐induced JNK1 phosphorylation inhibits hedgehog signalling and osteoblast differentiation. (8th September 2014)

• Record Type: Journal Article
• Authors: Shiohama, Tadashi; Fujii, Katsunori; Uchikawa, Hideki; Takatani, Tomozumi; Mizuochi, Hiromi; Kohno, Yoichi
• Is Part Of: Cell biology international reports. Volume 21:Number 2(2014)
• Page Start: 53
• Page End: 62
• Publication Date: 2014-09-08
• Subjects: Cytology -- Periodicals; 571.605
• DOI: 10.1002/cbi3.10017
• Languages: English
• ISSNs: 2041-5346

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="cbi310017-sec-0001" sec-type="section"> <p>Oxidative stress has been progressively recognised as a key player in the development of osteoporosis. Although oxidative stress induces osteoporosis partly through inhibition of hedgehog signalling, the details of the signal interaction remain unclear. To elucidate this mechanism, we investigated osteoblast differentiation in C3H10T1/2 cells, murine embryonic mesenchymal cells, with recombinant sonic hedgehog (shh) in the presence or absence of hydrogen peroxide, and examined <italic>Gli</italic> transcriptional activity, with a focus on the interaction with mitogen‐activated protein kinases (MAPKs) as possible mediators. The transcription of <italic>Gli1</italic>, <italic>Ptch1b</italic>, <italic>Alp</italic> and <italic>Bsp</italic> was facilitated by shh and strongly inhibited by oxidative stress with the hydrogen peroxide treatment; however, the other <italic>Gli</italic> isoforms, <italic>Bmp2</italic>, <italic>Runx2</italic> and <italic>Osx</italic>, were unaffected. Oxidative stress also facilitated the phosphorylation of JNK1 and p38. Anisomycin treatment as a JNK activator or transient overexpression of the constitutive JNK1 active form inhibited hedgehog activity. Interestingly, the inhibitory effect of hydrogen peroxide on hedgehog signalling was blocked by a JNK inhibitor, but not by a p38 inhibitor. Osteoblast differentiation determined by calcium staining was, in part, rescued from oxidative stress by the JNK inhibitor. These findings suggest that oxidative stress inhibits hedgehog signalling and subsequent osteoblast differentiation through an interaction between phospho‐JNK1 and GLI1.</p> </sec> </abstract>