Circulating Osteoblast-Lineage Cells in Humans
Abstract
BACKGROUND: Although current evidence suggests that only a minuscule number of osteoblast-lineage cells are present in peripheral blood, we hypothesized that such cells circulate but that their concentration has been vastly underestimated owing to the use of assays that required adherence to plastic. We further reasoned that the concentration of these cells is elevated during times of increased bone formation, such as during pubertal growth. METHODS: We used flow cytometry with antibodies to bone-specific proteins to identify circulating osteoblast-lineage cells in 11 adolescent males and 11 adult males (mean [+/-SD] age, 14.5+/-0.7 vs. 37.7+/-7.6 years). Gene expression and in vitro and in vivo bone-forming assays were used to establish the osteoblastic lineage of sorted cells. RESULTS: Cells positive for osteocalcin and cells positive for bone-specific alkaline phosphatase were detected in the peripheral blood of adult subjects (1 to 2 percent of mononuclear cells). There were more than five times as many cells positive for osteocalcin in the circulation of adolescent boys (whose markers of bone formation were clearly increased as a result of pubertal growth) as compared with adult subjects (P<0.001). The percentage of cells positive for osteocalcin correlated with markers of bone formation. Sorted osteocalcin-positive cells expressed osteoblastic genes, formed mineralized nodules in vitro, and formed bone in an in vivo transplantation assay. Increased values were also found in three adults with recent fractures. CONCLUSIONS: Osteoblast-lineage cells circulate in physiologically significant numbers, correlate with markers of bone formation, and are markedly higher during pubertal growth; therefore, they may represent a previously unrecognized circulatory component to the process of bone formation.
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Circulating osteogenic cells circulate in physiologically significant numbers, correlate with markers of bone formation, and increase during bone growth.
“Cells with multiple potential differentiation routes similar to those of BMSCs can enter the circulation, and although the mechanism by which they enter the circulation is unclear, they circulate in physiologically significant numbers, correlate with markers of bone formation and increase during bone growth.127”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [127]
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- Authors
- Eghbali-Fatourechi, G. Z., Lamsam, J., Fraser, D., Nagel, D., Riggs, B. L., & Khosla, S.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Khosla, Sundeep
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2005-05-12
- Volume
- 352
- Issue
- 19
- Pages
- 1959-1966
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2052673490
- Cited by
- 418
- References
- 20
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 7 · 2023: 13 · 2022: 11 · 2021: 20 · 2020: 13 · 2019: 18 · 2018: 16 · 2017: 15 · 2016: 11 · 2015: 20 · 2014: 25 · 2013: 30 · 2012: 31
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG024901, P01AG004875, R21AG024901, AG004875)
- National Center for Research Resources (M01-RR00 585, M01RR000585)
- 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
- osteocalcin, bone-specific alkaline phosphatase, bone formation, pubertal growth, peripheral blood mononuclear cells, bone formation markers
- MeSH terms
- Adolescent, Adult, Aging, Alkaline Phosphatase, Animals, Flow Cytometry, Genetic Markers, Humans, Insulin-Like Growth Factor I, Male, Middle Aged, Osteoblasts, Osteogenesis, Osteocalcin, Gene Expression, Bone Remodeling, Immunocompromised Host, Cell Lineage, Reverse Transcriptase Polymerase Chain Reaction, Collagen Type II, Fractures, Bone, Mice
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