Beier Eric E, Holz Jonathan D, Sheu Tzong-Jen, Puzas J Edward
*Center for Musculoskeletal Research; Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, 14624; and.
*Center for Musculoskeletal Research; Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, 14624; and Department of Math and Natural Sciences, D'Youville College, Buffalo, New York, 14201.
Toxicol Sci. 2016 Feb;149(2):277-88. doi: 10.1093/toxsci/kfv234. Epub 2015 Oct 30.
The heavy metal lead (Pb) has a deleterious effect on skeletal health. Because bone mass is maintained through a balance of bone formation and resorption, it is important to understand the effect of Pb levels on osteoblastic and osteoclastic activity. Pb exposure is associated with low bone mass in animal models and human populations; however, the correlation between Pb dosing and corresponding bone mass has been poorly explored. Thus, mice were exposed to increasing Pb and at higher levels (500 ppm), there was unexpectedly an increase in femur-tibial bone mass by 3 months of age. This is contrary to several studies alluded to earlier. Increased bone volume (BV) was accompanied by a significant increase in cortical thickness of the femur and trabecular bone that extended beyond the epiphyseal area into the marrow cavity. Subsequent evaluations revealed an increase in osteoclast numbers with high Pb exposure, but a deficiency in osteoclastic activity. These findings were substantiated by observed increases in levels of the resorption-altering hormones calcitonin and estrogen. In addition we found that pro-osteoclastic nuclear factor-kappa beta (NF-κB) pathway activity was dose dependently elevated with Pb, both in vivo and in vitro. However, the ability of osteoclasts to resorb bone was depressed in the presence of Pb in media and within test bone wafers. These findings indicate that exposure to high Pb levels disrupts early life bone accrual that may involve a disruption of osteoclast activity. This study accentuates the dose dependent variation in Pb exposure and consequent effects on skeletal health.
重金属铅（Pb）对骨骼健康具有有害影响。由于骨量是通过骨形成和骨吸收之间的平衡来维持的，因此了解铅水平对成骨细胞和破骨细胞活性的影响非常重要。在动物模型和人群中，铅暴露与低骨量有关；然而，铅剂量与相应骨量之间的相关性尚未得到充分研究。因此，让小鼠接触逐渐增加的铅，在较高水平（500 ppm）时，到3月龄时股骨-胫骨骨量意外增加。这与之前提到的几项研究相反。骨体积（BV）增加伴随着股骨皮质厚度和小梁骨的显著增加，小梁骨延伸至骨骺区域之外进入骨髓腔。随后的评估显示，高铅暴露会使破骨细胞数量增加，但破骨细胞活性不足。降钙素和雌激素等影响骨吸收的激素水平升高证实了这些发现。此外，我们发现促破骨细胞核因子-κB（NF-κB）信号通路活性在体内和体外均随铅剂量依赖性升高。然而，在培养基和测试骨片中存在铅的情况下，破骨细胞吸收骨的能力受到抑制。这些发现表明，高铅暴露会破坏早期生命中的骨量积累，这可能涉及破骨细胞活性的破坏。这项研究强调了铅暴露的剂量依赖性变化及其对骨骼健康的后续影响。
