Circulating Osteogenic Precursor Cells in Type 2 Diabetes Mellitus

• Published in: The journal of clinical endocrinology and metabolism Vol. 97; no. 9; pp. 3240 - 3250
• Main Authors: Manavalan, J. S., Cremers, S., Dempster, D. W., Zhou, H., Dworakowski, E., Kode, A., Kousteni, S., Rubin, M. R.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.09.2012; Endocrine Society
• Subjects: Biological and medical sciences; Biomarkers; Blood Glucose - metabolism; Body Mass Index; Bone and Bones - anatomy & histology; Bone Density - physiology; Bone Development - physiology; Bone growth; Bone Remodeling - physiology; Bone turnover; Cbfa-1 protein; Cross-Sectional Studies; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrine Research; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Flow Cytometry; Fractures; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression Regulation; Humans; Leukocytes (mononuclear); Male; Medical sciences; Middle Aged; Osteoblasts; Osteocalcin; Osteocalcin - blood; Osteogenesis; Oxidative stress; Oxidative Stress - physiology; Peripheral blood mononuclear cells; Post-menopause; Postmenopause - physiology; Stem Cells - physiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Type 2 diabetes; Obesity; Nutrition; Nutrition disorder; Precursor cell; Metabolic diseases; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2012-1546

Context: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.Patients, Design, and Setting:Eighteen postmenopausal women with T2D and 27 controls participated in this cross-sectional study at a clinical research center.Main Outcome Measures: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 μm3/um2 · 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 p66Shc 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.