HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 9, 8523-8530, March 4, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/9/8523    most recent M409442200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Ikeda, R. Articles by Inoue, I. Search for Related Content PubMed PubMed Citation Articles by Ikeda, R. Articles by Inoue, I. Social Bookmarking                      What's this?

The Promyelotic Leukemia Zinc Finger Promotes Osteoblastic Differentiation of Human Mesenchymal Stem Cells as an Upstream Regulator of CBFA1^*

Ryuji Ikeda, Kenichi Yoshida, So Tsukahara, Yoshiko Sakamoto, Hiroshi Tanaka, Ken-Ichi Furukawa¶, and Ituro Inoue||**

From the Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan, the Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube 755-8505, Japan, the ^¶Department of Pharmacology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan, and ^||Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, 4-1-8 Honmachi, Kawaguchi 332-0012, Japan

Ossification of the posterior longitudinal ligament of the spine (OPLL) is the leading cause of myelopathy in Japan and is diagnosed by ectopic bone formation in the paravertebral ligament. OPLL is a systemic high bone mass disease with a strong genetic background. To detect genes relevant to the pathogenesis of OPLL, we performed a cDNA microarray analysis of systematic gene expression profiles during the osteoblastic differentiation of ligament cells from OPLL patients (OPLL cells), patients with a disorder called ossification of yellow ligament (OYL), and non-OPLL controls together with human mesenchymal stem cells (hMSCs) after stimulating them with osteogenic differentiation medium (OS). Twenty-four genes were up-regulated during osteoblastic differentiation in OPLL cells. Zinc finger protein 145 (promyelotic leukemia zinc finger or PLZF) was one of the highly expressed genes during osteoblastic differentiation in all the cells examined. We investigated the roles of PLZF in the regulation of osteoblastic differentiation of hMSCs and C2C12 cells. Small interfering RNA-mediated gene silencing of PLZF resulted in a reduction in the expression of osteoblast-specific genes such as the alkaline phosphatase, collagen 1A1 (Col1a1), Runx2/core-binding factor 1 (Cbfa1), and osteocalcin genes, even in the presence of OS in hMSCs. The expression of PLZF was unaffected by the addition of bone morphogenetic protein 2 (BMP-2), and the expression of BMP-2 was not affected by PLZF in hMSCs. In C2C12 cells, overexpression of PLZF increased the expression of Cbfa1 and Col1a1; on the other hand, the overexpression of CBFA1 did not affect the expression of Plzf. These findings indicate that PLZF plays important roles in early osteoblastic differentiation as an upstream regulator of CBFA1 and thereby might participate in promoting the ossification of spinal ligament cells in OPLL patients.

Received for publication, August 17, 2004 , and in revised form, December 20, 2004.

^* This work was supported in part by a Research Grant for Specific Diseases from the Japan Foundation of Aging and Health of the Ministry of Public Health and Welfare and a Grant-in-Aid for scientific research from the Japanese Ministry of Education, Science, Sports, and Culture (to I. I). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contain Supplemental Table I on the oligonucleotide primers used in this study.

^** To whom correspondence should be addressed. Tel.: 81-3-5449-5325; Fax: 81-3-5449-5764; E-mail: ituro{at}ims.u-tokyo.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Kita, T. Kimura, N. Nakamura, H. Yoshikawa, and T. Nakano PI3K/Akt signaling as a key regulatory pathway for chondrocyte terminal differentiation. Genes Cells, August 1, 2008; 13(8): 839 - 850. [Abstract] [Full Text] [PDF]

				W. Zhu, O. Boachie-Adjei, B. A. Rawlins, B. Frenkel, A. L. Boskey, L. B. Ivashkiv, and C. P. Blobel A Novel Regulatory Role for Stromal-derived Factor-1 Signaling in Bone Morphogenic Protein-2 Osteogenic Differentiation of Mesenchymal C2C12 Cells J. Biol. Chem., June 29, 2007; 282(26): 18676 - 18685. [Abstract] [Full Text] [PDF]

				Y. Zhao and S. Ding A high-throughput siRNA library screen identifies osteogenic suppressors in human mesenchymal stem cells PNAS, June 5, 2007; 104(23): 9673 - 9678. [Abstract] [Full Text] [PDF]

				T. M. Liu, M. Martina, D. W. Hutmacher, J. H. P. Hui, E. H. Lee, and B. Lim Identification of Common Pathways Mediating Differentiation of Bone Marrow- and Adipose Tissue-Derived Human Mesenchymal Stem Cells into Three Mesenchymal Lineages Stem Cells, March 1, 2007; 25(3): 750 - 760. [Abstract] [Full Text] [PDF]

				E. Seeman and G. J. Strewler Clinical and Basic Research Papers - February 2005 Selections IBMS BoneKEy, March 1, 2005; 2(3): 1 - 5. [Full Text] [PDF]