Absence of Glutamine Supplementation Prevents Differentiation of Murine Calvarial Osteoblasts to a Mineralizing Phenotype
Abstract
Osteoblasts in vitro differentiate from a proliferating to a mineralizing phenotype upon transfer to a medium rich in beta-glycerophosphate and ascorbic acid. The nutritional requirements of the cells at different stages of this differentiation process are not known. In other cell types, nutritional supplementation during surgery can improve the outcome in terms of speed of patient recovery and prognosis. There is therefore the potential for supplementation at the site of fracture repair or bone grafting with critical osteoblast nutritional factors to potentially accelerate healing. In this study we investigate which common cell nutrients are required for the proliferating and mineralizing stages of osteoblast differentiation. Medium containing 5.5 mM glucose was sufficient to achieve maximal proliferation of primary calvarial osteoblasts and human osteoblast cell lines, with some added benefit of additional glutamine supplementation. However, when cells were stimulated to mineralize, glucose was insufficient to support their energetic requirements. Only when cells were supplemented with glucose together with glutamine were high levels of osteocalcin expression observed together with mineralized nodules in culture, suggesting that this would be a useful combination to assess in cultures of primary human osteoblasts to determine whether it may have beneficial effects during fracture surgery, bone grafting, and fixation of uncemented arthroplasty implants.
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When osteoblasts are induced to undergo mineralization, glucose alone is inadequate to fulfill their energy needs; the degree of mineralization only increases when cells are provided with glucose and glutamine supplementation.
“It has been observed that when osteoblasts are induced to undergo mineralization, glucose alone is inadequate to fulfill their energy needs. The degree of mineralization only increases when cells are provided with glucose and glutamine supplementation [64, 65].”
From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [64]
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- Authors
- Brown, P. M., Hutchison, J. D., & Crockett, J. C.
- Affiliations
- University of Aberdeen (GB)
- Corresponding author
- Crockett, Julie C.
- ORCID
- Brown, Philip M.
- Venue
- Calcified Tissue International
- Published
- 2011-10-05
- Volume
- 89
- Issue
- 6
- Pages
- 472-482
- ISSN
- 0171-967X (ISSN-L)
- 1432-0827
- OpenAlex
- W2066217988
- Cited by
- 37
- References
- 47
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 2 · 2014: 4
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Calcified Tissue International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Versus Arthritis
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Keywords
- glutamine supplementation, osteogenic differentiation, osteoblast mineralization, calvarial osteoblasts, glucose, osteocalcin, bone regeneration, fracture healing, bone grafting, cell proliferation
- MeSH terms
- Animals, Calcification, Physiologic, Cell Differentiation, Cells, Cultured, Glutamine, Humans, Mice, Inbred C57BL, Osteoblasts, Phenotype, Skull, Osteocalcin, Pyruvic Acid, Mice
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