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J. Biol. Chem., Vol. 278, Issue 19, 17360-17367, May 9, 2003

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Expression of Galectin-3 in Skeletal Tissues Is Controlled by Runx2^*

Michael Stock^§, Henning Schäfer, Sigmar Stricker^¶, Gerhard Gross, Stefan Mundlos^¶, and Florian Otto^**

From the  Division of Hematology/Oncology, Medical Center and the ^§ Institute for Biology I, University of Freiburg, 79106 Freiburg, Germany, the ^¶ Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany, and the  Gesellschaft für Biotechnologische Forschung, 38124 Braunschweig, Germany

The -galatoside-specific lectin galectin-3 is expressed in vivo in osteoblasts as well as in epiphyseal cartilage. Here we show that in vitro, galectin-3 expression is up-regulated in the preosteoblastic cell line MC3T3-E1 during the matrix maturation stage of the osteoblast developmental sequence. Expression persists into late differentiation stages when the mature osteoblastic phenotype is established. The skeletal expression pattern of galectin-3 overlaps at many sites with that of the transcription factor Runx2. Runx2 is a key regulator of osteoblast development and necessary for chondrocyte differentiation in the growth plate. Both human and mouse galectin-3 promoters contain putative Runx-binding sites. The constitutive or inducible forced expression of Runx2 is sufficient for the onset of galectin-3 transcription in the mesenchymal precursor cell line C3H10T1/2. Moreover, Runx2 is able to bind to at least two sites in the galectin-3 promoter region. The crucial role of Runx2 was confirmed in Runx2-deficient mice, which are devoid of galectin-3 expression in skeletal cells. The overlapping expression pattern of galectin-3 with the other two members of the Runt family of transcription factors (Runx1 and Runx3) points to a potential regulation of the galectin-3 gene (LGALS3) by these factors in hematopoietic, skin, and dorsal root ganglial cells.

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