title: Circulating osteogenic precursor cells in type 2 diabetes mellitus.
abstract: BACKGROUND
  Type 2 diabetes mellitus (T2D) is associated with an increased risk of fractures and low bone formation. However, the mechanism for the low bone formation is not well understood. Recently, circulating osteogenic precursor (COP) cells, which contribute to bone formation, have been characterized in the peripheral circulation.
  
  
  OBJECTIVE
  Our objective was to characterize the number and maturity of COP cells in T2D.
  
  
  METHODS
  Eighteen postmenopausal women with T2D and 27 controls participated in this cross-sectional study at a clinical research center.
  
  
  METHODS
  COP cells were characterized using flow cytometry and antibodies against osteocalcin (OCN) and early stem cell markers. Histomorphometric (n = 9) and molecular (n=14) indices of bone turnover and oxidative stress were also measured.
  
  
  RESULTS
  The percentage of OCN(+) cells in peripheral blood mononuclear cells was lower in T2D (0.8 ± 0.2 vs. 1.6 ± 0.4%; P < 0.0001), whereas the percentage of OCN(+) cells coexpressing the early marker CD146 was increased (OCN(+)/CD146(+): 33.3 ± 7 vs. 12.0 ± 4%; P < 0.0001). Reduced histomorphometric indices of bone formation were observed in T2D subjects, including mineralizing surface (2.65 ± 1.9 vs. 7.58 ± 2.4%, P = 0.02), bone formation rate (0.01 ± 0.1 vs. 0.05 ±0.2 μm(3)/um(2) · d, P = 0.02), and osteoblast surface (1.23 ±0.9 vs. 4.60 ± 2.5%, P = 0.03). T2D subjects also had reduced molecular expression of the osteoblast regulator gene Runx2 but increased expression of the oxidative stress markers p66(Shc) and SOD2.
  
  
  CONCLUSIONS
  Circulating OCN(+) cells were decreased in T2D, whereas OCN(+)/CD146(+) cells were increased. Histomorphometric indices of bone formation were decreased in T2D, as was molecular expression of osteoblastic activity. Stimulation of bone formation may have beneficial therapeutic skeletal consequences in T2D.
authors: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors: J S
authors: JS
authors: Manavalan
authors: S
authors: S
authors: Cremers
authors: D W
authors: DW
authors: Dempster
authors: H
authors: H
authors: Zhou
authors: E
authors: E
authors: Dworakowski
authors: A
authors: A
authors: Kode
authors: S
authors: S
authors: Kousteni
authors: M R
authors: MR
authors: Rubin
mesh_terms: D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D015519:Bone Density / Q000502:physiology; D001846:Bone Development / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology; D001842:Bone and Bones / Q000033:anatomy & histology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology; D017698:Postmenopause / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D015675:Osteocalcin