QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 10 July 2007
doi: 10.1242/jcs.005090

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.005090v1 120/15/2565    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ali, Md. M. Articles by Kawashima, H. Search for Related Content PubMed PubMed Citation Articles by Ali, Md. M. Articles by Kawashima, H.

PIASx is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts

¹ Division of Cell Biology and Molecular Pharmacology, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata-city, Niigata 951-8514, Japan
² Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata-city, Niigata 951-8514, Japan
³ Department of Molecular Pharmacology and 21st Century Center of Excellence (COE) Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Medical Research Institute, Tokyo Medical and Dental University, Kanda-Surugadai 2-3-10, Chiyoda-ku, Tokyo 101-0062, Japan.

^* Author for correspondence (e-mail: kawashim{at}dent.niigata-u.ac.jp)

Accepted 18 May 2007

We recently reported that tensile stress induces osteoblast differentiation and osteogenesis in the mouse calvarial suture in vitro. Using this experimental system, we identified PIASx, a splice isoform of Pias2, as one of the genes most highly upregulated by tensile stress. Further study using cell culture revealed that this upregulation was transient and was accompanied by upregulation of other differentiation markers, including osterix, whereas expression of Runx2 was unaffected. Runx2 and osterix are the two master proteins controlling osteoblast differentiation, with Runx2 being upstream of osterix. Targeted knockdown of PIASx by small interfering RNA (siRNA) markedly suppressed osteoblastic differentiation and matrix mineralization, whereas transient overexpression of PIASx caused the exact opposite effects. Regardless of PIASx expression level, Runx2 expression remained constant. Reporter assays demonstrated that osterix enhanced its own promoter activity, which was further stimulated by PIASx but not by its sumoylation-defective mutant. NFATc1 and NFATc3 additionally increased osterix transcriptional activity when co-transfected with PIASx. Because osterix has no consensus motif for sumoylation, other proteins are probably involved in the PIASx-mediated activation and NFAT proteins may be among such targets. This study provides the first line of evidence that PIASx is indispensable for osteoblast differentiation and matrix mineralization, and that this signaling molecule is located between Runx2 and osterix.

Key words: PIASx, Osterix, Mineralization, Osteoblast

This article has been cited by other articles:

				S.-L. Cheng, J.-S. Shao, J. Cai, O. L. Sierra, and D. A. Towler Msx2 Exerts Bone Anabolism via Canonical Wnt Signaling J. Biol. Chem., July 18, 2008; 283(29): 20505 - 20522. [Abstract] [Full Text] [PDF]