title: Regulation of CXCL12 expression by canonical Wnt signaling in bone marrow stromal cells.
abstract: CXCL12 (stromal cell-derived factor-1, SDF-1), produced by stromal and endothelial cells including cells of the bone marrow, binds to its receptor CXCR4 and this axis regulates hematopoietic cell trafficking. Recently, osteoclast precursor cells were found to express CXCR4 and a potential role for the CXCL12-CXCR4 axis during osteoclast precursor cell recruitment/retention and development was proposed as a regulator of bone resorption. We examined the role of canonical Wnt signaling in regulating the expression of CXCL12 in bone marrow stromal cells. In mouse stromal ST2 cells, CXCL12 mRNA was expressed, while its expression was reduced in Wnt3a over-expressing ST2 (Wnt3a-ST2) cells or by treatment with lithium chloride (LiCl). Wnt3a decreased CXCL12 levels in culture supernatants from mouse bone marrow stromal cells. The culture supernatant from Wnt3a-ST2 cells also reduced migratory activity of bone marrow-derived cells in a Transwell migration assay. Silencing of glycogen synthase kinase-3β decreased CXCL12 expression, suggesting that the canonical Wnt signaling pathway regulates CXCL12 expression. In a transfection assay, LiCl down-regulated the activity of a reporter gene, a 1.8kb fragment of the 5'-flanking region of the CXCL12 gene. These results show that canonical Wnt signaling regulates CXCL12 gene expression at the transcriptional level, and this is the first study linking chemokine expression to canonical Wnt signaling.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Dental Medicine, Hokkaido University, North 13, West 7, Sapporo 060-8586, Japan. mtamura@den.hokudai.ac.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Tamura
authors.forename: Mari M
authors.initials: MM
authors.lastname: Sato
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nashimoto
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002460:Cell Line; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000235:genetics*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000172:deficiency / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D010010:Osteoclasts / Q000166:cytology; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: D054377:Chemokine CXCL12; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3