Energy Metabolism of the Osteoblast: Implications for Osteoporosis
Open accessAbstract
Osteoblasts, the bone-forming cells of the remodeling unit, are essential for growth and maintenance of the skeleton. Clinical disorders of substrate availability (e.g., diabetes mellitus, anorexia nervosa, and aging) cause osteoblast dysfunction, ultimately leading to skeletal fragility and osteoporotic fractures. Conversely, anabolic treatments for osteoporosis enhance the work of the osteoblast by altering osteoblast metabolism. Emerging evidence supports glycolysis as the major metabolic pathway to meet ATP demand during osteoblast differentiation. Glut1 and Glut3 are the principal transporters of glucose in osteoblasts, although Glut4 has also been implicated. Wnt signaling induces osteoblast differentiation and activates glycolysis through mammalian target of rapamycin, whereas parathyroid hormone stimulates glycolysis through induction of insulin-like growth factor-I. Glutamine is an alternate fuel source for osteogenesis via the tricarboxylic acid cycle, and fatty acids can be metabolized to generate ATP via oxidative phosphorylation although temporal specificity has not been established. More studies with new model systems are needed to fully understand how the osteoblast utilizes fuel substrates in health and disease and how that impacts metabolic bone diseases.
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Both bone modeling and remodeling necessitate the manufacture of collagen and other matrix proteins by osteoblasts, thereby consuming a substantial quantity of ATP.
“In fact, both the modeling and remodeling processes necessitate the manufacture of collagen and other matrix proteins by osteoblasts (OBs), thereby consuming a substantial quantity of energy in the form of adenosine triphosphate (ATP) [44, 45].”
From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [44]
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- Authors
- Lee, W.-C., Guntur, A. R., Long, F., & Rosen, C. J.
- Affiliations
- Washington University in St. Louis (US)
- Maine Medical Center Research Institute (US)
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2017-05-01
- Volume
- 38
- Issue
- 3
- Pages
- 255-266
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- PMC
- PMC5460680
- OpenAlex
- W2610405998
- Cited by
- 443
- References
- 14
- Citations by year
- 2026: 46 · 2025: 74 · 2024: 51 · 2023: 67 · 2022: 57 · 2021: 56 · 2020: 38 · 2019: 34 · 2018: 15 · 2017: 4
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Maine Medical Center Research Institute
- National Institutes of Health
- National Institute of General Medical Sciences (P20GM103465)
- National Institute of Diabetes and Digestive and Kidney Diseases (R21DK092750)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR055923, R21AR066120, R01AR060456, R21AR071739, R03AR068095)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Keywords
- osteoporosis, glycolysis, glucose transporters, GLUT1, GLUT3, GLUT4, Wnt signaling, mTOR, parathyroid hormone, insulin-like growth factor I, glutamine metabolism, TCA cycle, fatty acid oxidation, oxidative phosphorylation, osteogenic differentiation, bone remodeling, metabolic bone disease, osteoporotic fractures
- MeSH terms
- Animals, Cell Differentiation, Energy Metabolism, Humans, Osteoblasts, Osteogenesis, Osteoporosis, Signal Transduction, Glucose Transport Proteins, Facilitative, Wnt Signaling Pathway
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