Expression of galectin-3 in skeletal tissues is controlled by Runx2.
The beta-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.
Stock
Michael
M
Division of Hematology/Oncology, Medical Center, University of Freiburg, 79106 Freiburg, Germany.
Schäfer
Henning
H
Stricker
Sigmar
S
Gross
Gerhard
G
Mundlos
Stefan
S
Otto
Florian
F
D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D037502:Galectin 3 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D037502:Galectin 3; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C493726:Runx1 protein, mouse; C493730:Runx3 protein, mouse; D014157:Transcription Factors