Department of Clinical and Experimental Medicine, Metabolic Division, University of Padova, Medical School, Padova, Italy.
Circ Res. 2011 Apr 29;108(9):1112-21. doi: 10.1161/CIRCRESAHA.110.234088. Epub 2011 Mar 10.
Acquisition of a procalcific phenotype by resident or circulating cells is important for calcification of atherosclerotic plaques, which is common in diabetes.
We aim to identify and characterize circulating calcifying cells, and to delineate a pathophysiological role for these cells in type 2 diabetes.
We demonstrate for the first time that a distinct subpopulation of circulating cells expressing osteocalcin and bone alkaline phosphatase (OC(+)BAP(+)) has procalcific activity in vitro and in vivo. The study of naïve patients with chronic myeloid leukemia indicated that OC(+)BAP(+) cells have a myeloid origin. Myeloid calcifying OC(+)BAP(+) cells (MCCs) could be differentiated from peripheral blood mononuclear cells, and generation of MCCs was closely associated with expression of the osteogenic transcription factor Runx2. In gender-mismatched bone marrow-transplanted humans, circulating MCCs had a much longer half-life compared with OC(-)BAP(-) cells, suggesting they belong to a stable cell repertoire. The percentage of MCCs was higher in peripheral blood and bone marrow of type 2 diabetic patients compared with controls but was lowered toward normal levels by optimization of glycemic control. Furthermore, diabetic carotid endoarterectomy specimens showed higher degree of calcification and amounts of cells expressing OC and BAP in the α-smooth muscle actin-negative areas surrounding calcified nodules, where CD68(+) macrophages colocalize. High glucose increased calcification by MCCs in vitro, and hypoxia may regulate MCC generation in vitro and in vivo.
These data identify a novel type of blood-derived procalcific cells potentially involved in atherosclerotic calcification of diabetic patients.
在动脉粥样硬化斑块的钙化中，驻留细胞或循环细胞获得成骨表型是很重要的，而糖尿病患者中这种情况很常见。
我们旨在鉴定和描述循环钙化细胞，并阐明这些细胞在 2 型糖尿病中的病理生理作用。
我们首次证明，一种表达骨钙素和骨碱性磷酸酶的循环细胞亚群（OC(+)BAP(+)）具有体外和体内的成骨活性。对慢性髓系白血病的初治患者的研究表明，OC(+)BAP(+)细胞具有髓系起源。骨髓来源的 OC(+)BAP(+)细胞（MCCs）可以从外周血单核细胞中分化而来，并且 MCC 的生成与成骨转录因子 Runx2 的表达密切相关。在性别不匹配的骨髓移植人类中，与 OC(-)BAP(-)细胞相比，循环 MCC 的半衰期要长得多，这表明它们属于稳定的细胞群。与对照组相比，2 型糖尿病患者的外周血和骨髓中的 MCC 百分比更高，但通过优化血糖控制可使其降低至正常水平。此外，糖尿病颈动脉内膜切除术标本显示，在围绕钙化结节的α-平滑肌肌动蛋白阴性区域，钙化程度更高，并且表达 OC 和 BAP 的细胞数量更多，其中 CD68(+)巨噬细胞发生共定位。高葡萄糖可增加 MCC 的体外钙化，而低氧可能调节体外和体内的 MCC 生成。
这些数据确定了一种新型的血液来源的促钙化细胞，可能与糖尿病患者的动脉粥样硬化钙化有关。
