Regulation of CXCL12 expression by canonical Wnt signaling in bone marrow stromal cells
Open accessAbstract
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.
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Circulating CXCR4-expressing HSCs are attracted to bone surfaces by gradients of SDF-1 (CXCL12) secreted by CXCR4+ CD45−, stromal, and endothelial marrow cells.
“Circulating CXCR4-expressing HSCs are attracted to bone surfaces by gradients of SDF-1 (CXCL12) secreted by CXCR4+ CD45−, stromal, and endothelial marrow cells [14,17].”
From Osteoclasts and Microgravity (2020) · cites this paper as [17]
The Introduction says marrow stromal and endothelial cells produce CXCL12, HSCs express its receptor CXCR4, and CXCL12–CXCR4 interactions help maintain HSC niches on bone’s endosteal surface. The Discussion describes CXCL12 as a chemoattractant. Neither section identifies CXCR4+ CD45− cells as CXCL12 producers or establishes that gradients attract circulating HSCs toward bone surfaces. (LLM, conf=0.87)
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Smith, J. K. (2020) · Life · doi:10.3390/life10090207 · Cited by 52 · see citing works
“Circulating CXCR4-expressing HSCs are attracted to bone surfaces by gradients of SDF-1 (CXCL12) secreted by CXCR4+ CD45−, stromal, and endothelial marrow cells [14,17].”
BackgroundInteractions of B-lymphocytes and bone cells in health and disease
Grčević, D., Sanjay, A., & Lorenzo, J. (2023) · Bone · doi:10.1016/j.bone.2021.116296 · Cited by 36 · see citing works
- Authors
- Tamura, M., Sato, M. M., & Nashimoto, M.
- Affiliations
- Hokkaido University (JP)
- Niigata University of Pharmacy and Medical and Life Sciences (JP)
- Corresponding author
- Tamura, Masato
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 43
- Issue
- 5
- Pages
- 760-767
- ISSN
- 1357-2725 (ISSN-L)
- OpenAlex
- W2019894120
- Cited by
- 51
- References
- 0
- Citations by year
- 2025: 2 · 2024: 3 · 2022: 2 · 2021: 5 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 6 · 2015: 5 · 2014: 8 · 2013: 5 · 2012: 4
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (22390346)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- CXCL12, Wnt/β-catenin signaling, mesenchymal stem cells, Wnt3a, glycogen synthase kinase-3β, CXCR4, chemokine expression, transcriptional regulation, osteoclast precursor cells, bone resorption, lithium chloride
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Animals, Bone Marrow Cells, Cell Line, Cell Movement, Gene Expression Regulation, Osteoclasts, Promoter Regions, Genetic, Signal Transduction, Down-Regulation, Stromal Cells, Glycogen Synthase Kinase 3, Wnt Proteins, Mice, Chemokine CXCL12, Gene Knockdown Techniques, Wnt3 Protein, Wnt3A Protein
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