Biphasic regulation of glutamine consumption by WNT during osteoblast differentiation
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Osteoblasts are the principal bone forming cells. As such, osteoblasts have enhanced demand for amino acids to sustain high rates of matrix synthesis associated with bone formation. The precise systems utilized by osteoblasts to meet these synthetic demands are not well understood. WNT signaling is known to rapidly stimulate glutamine uptake during osteoblast differentiation. Using a cell biology approach, we identified two amino acid transporters, Slc7a7 and Slc1a5, as the primary transporters of glutamine in response to WNT. Slc1a5 mediates the majority of glutamine uptake, whereas Slc7a7 mediates the rapid increase in glutamine uptake in response to WNT. Mechanistically, WNT signals through the canonical/β-catenin dependent pathway to rapidly induce Slc7a7 expression. Conversely, Slc1a5 expression is regulated by the transcription factor ATF4 downstream of the mTORC1 pathway. Targeting either Slc1a5 or Slc7a7 using shRNA reduced WNT induced glutamine uptake and prevented osteoblast differentiation. Collectively these data highlight the critical nature of glutamine transport for WNT induced osteoblast differentiation.
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Glutamine is transported into cells through plasma-membrane glutamine transporters, specifically SLC1A5 (ASCT2), SLC7A7, and SLC38A2 (SNAT2).
“Gln is transported into the cells through plasma-membrane Gln transporters, specifically SLC1A5 (ASCT2), SLC7A7, and SLC38A2 (SNAT2) [46, 62].”
From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [62]
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Taurine transporter SLC6A6 expression promotes mesenchymal stromal cell function
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Nutrient uptake and metabolism in osteoblasts
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Self-citationDelayed skeletal development and IGF-1 deficiency in a mouse model of lysinuric protein intolerance
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Collagen-based Mineralization of Bones, Teeth, and Other Vertebrate Skeletal Tissues
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First person – Leyao Shen and Deepika Sharma
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The eutherian-specific histone H3.4 promotes germ cell development and reproductive fitness
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- Authors
- Shen, L., Sharma, D., Yu, Y., Long, F., & Karner, C.
- Affiliations
- Duke University (US)
- Children's Hospital of Philadelphia (US)
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2020-01-01
- Volume
- 134
- Issue
- 1
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- PMC
- PMC7823158
- OpenAlex
- W3110417971
- Cited by
- 61
- References
- 54
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 11 · 2023: 16 · 2022: 13 · 2021: 4
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AR060456, AR071967)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- glutamine uptake, Wnt signaling, osteogenic differentiation, SLC7A7, SLC1A5, amino acid transporters, β-catenin signaling, ATF4, mTORC1, bone formation, amino acid metabolism
- MeSH terms
- Cell Differentiation, Glutamine, Osteoblasts, Osteogenesis, beta Catenin, Wnt Signaling Pathway
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