Background Although current evidence suggests that only a minusculenumber of osteoblast-lineage cells are present in peripheralblood, we hypothesized that such cells circulate but that theirconcentration has been vastly underestimated owing to the useof assays that required adherence to plastic. We further reasonedthat the concentration of these cells is elevated during timesof increased bone formation, such as during pubertal growth.
Methods We used flow cytometry with antibodies to bone-specificproteins to identify circulating osteoblast-lineage cells in11 adolescent males and 11 adult males (mean [±SD] age,14.5±0.7 vs. 37.7±7.6 years). Gene expressionand in vitro and in vivo bone-forming assays were used to establishthe osteoblastic lineage of sorted cells.
Results Cells positive for osteocalcin and cells positive forbone-specific alkaline phosphatase were detected in the peripheralblood of adult subjects (1 to 2 percent of mononuclear cells).There were more than five times as many cells positive for osteocalcinin the circulation of adolescent boys (whose markers of boneformation were clearly increased as a result of pubertal growth)as compared with adult subjects (P<0.001). The percentageof cells positive for osteocalcin correlated with markers ofbone formation. Sorted osteocalcin-positive cells expressedosteoblastic genes, formed mineralized nodules in vitro, andformed bone in an in vivo transplantation assay. Increased valueswere also found in three adults with recent fractures.
Conclusions Osteoblast-lineage cells circulate in physiologicallysignificant numbers, correlate with markers of bone formation,and are markedly higher during pubertal growth; therefore, theymay represent a previously unrecognized circulatory componentto the process of bone formation.
Source Information
From the Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, Minn.
Address reprint requests to Dr. Khosla at the Endocrine Research Unit, Mayo Clinic College of Medicine, 200 First St., SW, 5-194 Joseph, Rochester, MN 55905, or at khosla.sundeep{at}mayo.edu.
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