Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Metabolism. 2012 Apr;61(4):569-76. doi: 10.1016/j.metabol.2011.09.006. Epub 2011 Nov 9.
In postmenopausal women, an association between reduced bone mineral density (BMD) and increased number of circulating osteoprogenitor cells (COPs) has been found. Although an increased thyroid function is associated with BMD, thyroid hormones stimulate osteoblast function in vitro. We investigated whether thyroid hormones within the reference range were correlated with the number of COPs and stimulate mineralization in vitro. The number of COPs, defined as CD34+/alkaline phosphatase (AP)+ or CD34+/osteocalcin (OCN)+ cells, was quantified by fluorescence-activated cell sorting (FACS) analysis in 150 euthyroid postmenopausal women. Participants underwent measurement of serum free thyroxine (FT4), thyroid-stimulating hormone levels, and femur BMD. CD34+ cells were isolated from healthy volunteers irrespective of AP or OCN expression, and the effect of triiodothyronine (0.5-10 pmol/L)) on their ability to form mineralized nodules in vitro was studied. The number of COPs was highest among women with high-normal FT4 levels (>1.09 ng/dL). The FT4 levels were correlated positively with circulating log-CD34+/AP+ (r = 0.32, P < .001) and log-CD34/OCN+ cells (r = 0.36, P < .001) and inversely with total femur BMD (r = -0.17, P = .036) but not with femoral neck BMD. In a multivariate analysis, the FT4 levels were positively correlated with the number of COPs, independent of age and BMD. The ability of CD34+ cells to form mineralized nodules increased after exposure from low up to high-normal triiodothyronine concentrations (P for trend = .003). Among euthyroid postmenopausal women, high-normal FT4 levels are correlated with an increased number of circulating immature osteoprogenitor cells and a very mild BMD reduction. Exposure of CD34+ cells to physiological triiodothyronine concentrations stimulates mineralization in vitro.
在绝经后妇女中，已经发现骨密度（BMD）降低与循环成骨祖细胞（COPs）数量增加之间存在关联。尽管甲状腺功能亢进与 BMD 相关，但甲状腺激素在体外刺激成骨细胞功能。我们研究了参考范围内的甲状腺激素是否与 COPs 数量相关，并刺激体外矿化。通过荧光激活细胞分选（FACS）分析，在 150 名甲状腺功能正常的绝经后妇女中定量测定 COPs 的数量，定义为 CD34+/碱性磷酸酶（AP）+或 CD34+/骨钙素（OCN）+细胞。参与者接受血清游离甲状腺素（FT4）、促甲状腺激素水平和股骨 BMD 的测量。从健康志愿者中分离出 CD34+细胞，无论其是否表达 AP 或 OCN，研究三碘甲状腺原氨酸（0.5-10 pmol/L）对其在体外形成矿化结节的能力的影响。FT4 水平较高（>1.09ng/dL）的女性中 COPs 数量最高。FT4 水平与循环对数 CD34+/AP+（r = 0.32，P<.001）和对数 CD34/OCN+细胞（r = 0.36，P<.001）呈正相关，与总股骨 BMD 呈负相关（r = -0.17，P =.036），但与股骨颈 BMD 无关。在多变量分析中，FT4 水平与 COPs 的数量呈正相关，与年龄和 BMD 无关。CD34+细胞形成矿化结节的能力在暴露于从低到正常三碘甲状腺原氨酸浓度时增加（P 趋势=.003）。在甲状腺功能正常的绝经后妇女中，正常高值 FT4 水平与循环未成熟成骨祖细胞数量增加和非常轻微的 BMD 降低相关。CD34+细胞暴露于生理三碘甲状腺原氨酸浓度可刺激体外矿化。
