Article
- The EMBO Journal (2005) 24, 3049 - 3056
- doi:10.1038/sj.emboj.7600773
Published online: 4 August 2005
Subject Categories:
Fhl2 deficiency results in osteopenia due to decreased activity of osteoblasts
Thomas Günther1, Cecilia Poli1, Judith M Müller1, Philip Catala-Lehnen2,3, Thorsten Schinke2,3, Na Yin1, Sandra Vomstein1, Michael Amling2,3 and Roland Schüle1
- Universitäts-Frauenklinik und Zentrum für Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany
- Department of Trauma, Hand and Reconstructive Surgery, Hamburg University School of Medicine, Hamburg, Germany
- Experimental Trauma Surgery and Skeletal Biology, Center for Biomechanics, Hamburg University School of Medicine, Hamburg, Germany
Correspondence to:
Roland Schüle, Zentrum für Klinische Forschung, Molekulare Gynäkologie, Universitäts-Frauenklinik, Breisacherstr. 66, 79106 Freiburg, Germany. Tel.: +49 761 270 6310; Fax: +49 761 270 6311; E-mail: roland.schuele@uniklinik-freiburg.de
Received 16 March 2005; Accepted 14 July 2005
Abstract
Osteoporosis is one of the major health problems today, yet little is known about the loss of bone mass caused by reduced activity of the bone-forming osteoblasts. Here we show that mice deficient for the transcriptional cofactor four and a half LIM domains 2 (Fhl2) exhibit a dramatic decrease of bone mass in both genders. Osteopenia is caused by a reduced bone formation rate that is solely due to the diminished activity of Fhl2-deficient osteoblasts, while their number remains unchanged. The number and activity of the bone-resorbing cells, the osteoclasts, is not altered. Enforced expression of Fhl2 in differentiated osteoblasts boosts mineralization in cell culture and, importantly, enhances bone formation in transgenic animals. Fhl2 increases the transcriptional activity of runt-related transcription factor 2 (Runx2), a key regulator of osteoblast function, and both proteins interact in vitro and in vivo. In summary, we present Fhl2-deficient mice as a unique model for osteopenia due to decreased osteoblast activity. Our data offer a novel concept to fight osteoporosis by modulating the anabolic activity of osteoblasts via Fhl2.
Keywords:
- bone formation,
- Fhl2,
- osteoblast,
- osteoporosis,
- Runx2
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