TY - JOUR
T1 - Characterization of circulating osteoblast lineage cells in humans
AU - Eghbali-Fatourechi, Guiti Z.
AU - Mödder, Ulrike I.L.
AU - Charatcharoenwitthaya, Natthinee
AU - Sanyal, Arunik
AU - Undale, Anita H.
AU - Clowes, Jackie A.
AU - Tarara, James E.
AU - Khosla, Sundeep
N1 - Funding Information:
We would like to thank Dr. B.L. Riggs for helpful comments and discussion. This work was supported by grants AG004875 and AG024901 (National Institute on Aging) and RR00585 from the National Institutes of Health.
PY - 2007/5
Y1 - 2007/5
N2 - We recently identified circulating osteoblastic cells using antibodies to osteocalcin (OCN) or alkaline phosphatase (AP). We now provide a more detailed characterization of these cells. Specifically, we demonstrate that 46% of OCN positive (OCNpos) cells express AP, and 37% also express the hematopoietic/endothelial marker CD34. Using two different anti-OCN antibodies and forward/side light scatter characteristics by flow cytometry, we find that OCNpos cells consist of two distinct populations: one population exhibits low forward/side scatter, consistent with a small cell phenotype with low granularity, and a second population has higher forward/side scatter (larger and more granular cell). The smaller, low granularity population also co-expresses CD34, whereas the larger, more granular cells are CD34 negative. Using samples from 26 male subjects aged 28 to 68 years, we demonstrate that the concentration of circulating OCNpos cells increases as a function of age (R = 0.59, P = 0.002). By contrast, CD34pos cells tend to decrease with age (R = - 0.31, P = 0.18); as a consequence, the ratio of OCNpos:CD34pos cells also increase significantly with age (R = 0.54, P = 0.022). These findings suggest significant overlap between circulating cells expressing OCN and those expressing the hematopoietic/endothelial marker CD34. Further studies are needed to define the precise role of circulating OCNpos cells not only in bone remodeling but rather also potentially in the response to vascular injury.
AB - We recently identified circulating osteoblastic cells using antibodies to osteocalcin (OCN) or alkaline phosphatase (AP). We now provide a more detailed characterization of these cells. Specifically, we demonstrate that 46% of OCN positive (OCNpos) cells express AP, and 37% also express the hematopoietic/endothelial marker CD34. Using two different anti-OCN antibodies and forward/side light scatter characteristics by flow cytometry, we find that OCNpos cells consist of two distinct populations: one population exhibits low forward/side scatter, consistent with a small cell phenotype with low granularity, and a second population has higher forward/side scatter (larger and more granular cell). The smaller, low granularity population also co-expresses CD34, whereas the larger, more granular cells are CD34 negative. Using samples from 26 male subjects aged 28 to 68 years, we demonstrate that the concentration of circulating OCNpos cells increases as a function of age (R = 0.59, P = 0.002). By contrast, CD34pos cells tend to decrease with age (R = - 0.31, P = 0.18); as a consequence, the ratio of OCNpos:CD34pos cells also increase significantly with age (R = 0.54, P = 0.022). These findings suggest significant overlap between circulating cells expressing OCN and those expressing the hematopoietic/endothelial marker CD34. Further studies are needed to define the precise role of circulating OCNpos cells not only in bone remodeling but rather also potentially in the response to vascular injury.
KW - Circulating
KW - Immunophenotyping
KW - Mesenchymal
KW - Osteocalcin
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U2 - 10.1016/j.bone.2006.12.064
DO - 10.1016/j.bone.2006.12.064
M3 - Article
C2 - 17320497
AN - SCOPUS:34047265510
SN - 8756-3282
VL - 40
SP - 1370
EP - 1377
JO - Bone
JF - Bone
IS - 5
ER -