Circulating osteoblast-lineage cells in humans.
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.
Eghbali-Fatourechi
Guiti Z
GZ
Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA.
Lamsam
Jesse
J
Fraser
Daniel
D
Nagel
David
D
Riggs
B Lawrence
BL
Khosla
Sundeep
S
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology; D000469:Alkaline Phosphatase / Q000097:blood* / Q000235:genetics / Q000276:immunology; D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D019070:Cell Lineage; D024043:Collagen Type II / Q000097:blood / Q000235:genetics; D005434:Flow Cytometry; D050723:Fractures, Bone / Q000097:blood; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D016867:Immunocompromised Host; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D051379:Mice; D008875:Middle Aged; D010006:Osteoblasts; D015675:Osteocalcin / Q000097:blood* / Q000235:genetics / Q000276:immunology; D010012:Osteogenesis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D024043:Collagen Type II; D005819:Genetic Markers; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase