Cited by 61Bone Metabolism and DiseasesAmino Acid Enzymes and MetabolismWnt/β-catenin signaling in development and cancer

Biphasic regulation of glutamine consumption by WNT during osteoblast differentiation

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Shen, Leyao, Sharma, Deepika, Yu, Yilin, Long, Fanxin, Karner, Courtney·2020·Journal of Cell Science

Abstract

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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Crossref · 10.1242/jcs.251645

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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
Published
2020-01-01
Volume
134
Issue
1
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
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
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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