Research article summary (published 30 Oct 2009):

Runx2 and bone morphogenic protein 2 regulate the expression of an alternative Lef1 transcript during osteoblast maturation.

Full Abstract

Lymphoid Enhancer Binding Factor (Lef) 1 is a transcriptional effector of the Wnt/Lrp5/beta-catenin signaling cascade, which regulates osteoblast differentiation, bone density, and skeletal strength. In this study, we describe the expression and function of an alternative Lef1 isoform in osseous cells. Lef1DeltaN is a naturally occurring isoform driven by a promoter (p2) within the intron between exons 3 and 4 of Lef1. Lef1DeltaN is induced during late osteoblast differentiation. This is converse to the expression pattern of the full-length Lef1 protein, which as we previously showed, decreases during differentiation. Agonists of osteoblast maturation differentially affected Lef1DeltaN expression. BMP2 stimulated Lef1DeltaN expression, whereas Wnt3a blocked basal and BMP2-induced expression of Lef1DeltaN transcripts during osteoblast differentiation. We determined that the Lef1DeltaN p2 promoter is active in osteoblasts and Runx2 regulates its activity. Stable overexpression of Lef1DeltaN in differentiating osteoblasts induced the expression of osteoblast differentiation genes, osteocalcin and type 1 collagen. Taken together, our results suggest Lef1DeltaN is a crucial regulator of terminal differentiation in osseous cells.

Author information

Author/s: Hoeppner, Luke H (LH); Secreto, Frank (F); Jensen, Eric D (ED); Li, Xiaodong (X); Kahler, Rachel A (RA); Westendorf, Jennifer J (JJ);

Affiliation: Graduate Program in Microbiology, Immunology and Cancer Biology, University of Minnesota, Minneapolis, MN, USA.

Grants: AR050074 (Agency:NIAMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Journal of cellular physiology (J Cell Physiol), published in United States. (Language: eng)

Reference: 2009-Nov; vol 221 (issue 2) : pp 480-9

Dates: Created 2009/08/27; Completed 2009/09/09;

PMID: 19650108, status: MEDLINE (last retrieval date: 9/9/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Alternative Splicing - genetics Animals Blotting, Northern Bone Morphogenetic Protein 2 - metabolism Cell Differentiation - genetics Cell Line Core Binding Factor Alpha 1 Subunit - metabolism Lymphoid Enhancer-Binding Factor 1 - genetics; metabolism

Mice Mutant Proteins - metabolism Mutation - genetics Osteoblasts - cytology; metabolism Osteocalcin - genetics; metabolism Promoter Regions, Genetic RNA, Messenger - genetics; metabolism Wnt Proteins - metabolism

Associated Chemicals: Bone Morphogenetic Protein 2 (0) ; Core Binding Factor Alpha 1 Subunit (0) ; Lymphoid Enhancer-Binding Factor 1 (0) ; Mutant Proteins (0) ; RNA, Messenger (0) ; Wnt Proteins (0) ; Wnt-3 protein (0) ; Osteocalcin (104982-03-8)

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