Costa-Rodrigues Joao, Rocha Isabel, Fernandes Maria H
Faculdade de Medicina Dentária, U. Porto, Rua Dr. Manuel Pereira da Silva, Porto, Portugal.
ESTSP-Escola Superior de Tecnologia da Saúde do Porto, Instituto Politécnico do Porto, Porto, Portugal.
J Cell Physiol. 2018 Feb;233(2):1029-1040. doi: 10.1002/jcp.25956. Epub 2017 Jun 5.
Cigarette smoke is associated to pathological weakening of bone tissue, being considered an important playmaker in conditions such as osteoporosis and periodontal bone loss. In addition, it is also associated with an increased risk of failure in bone regeneration strategies. The present work aimed to characterize the effects of nicotine on human osteoclastogenesis over a hydroxyapatite substrate. Osteoclast precursors were maintained in the absence or presence of the osteoclastogenesis enhancers M-CSF and RANKL, and were further treated with nicotine levels representative of the concentrations observed in the plasma and saliva of smokers. It was observed that nicotine at low concentrations elicit an increase in osteoclast differentiation, but only in the presence of M-CSF and RANKL it was also able to significantly increase the resorbing ability of osteoclasts. A slight downregulation of NFkB pathway and an increase in the production of TNF-α and, particularly PGE2, were involved in the observed effects of nicotine. At high concentrations, nicotine revealed cytotoxic effects, causing a decrease in cell density. In conclusion, nicotine at levels found in the plasma of the smokers, has the ability to act directly on osteoclast precursors, inducing its osteoclastogenic differentiation. The stimulatory behavior appears to be dependent on the stage of osteoclastic differentiation of the precursor cells, which means, in the absence of M-CSF and RANKL, it only favors the initial stages of osteoclast differentiation, while in the presence of the growth factors, a significant increase in their resorbing ability is also achieved.
香烟烟雾与骨组织的病理性减弱有关，被认为是骨质疏松症和牙周骨丢失等病症的重要影响因素。此外，它还与骨再生策略失败风险的增加有关。本研究旨在表征尼古丁对羟基磷灰石基质上人类破骨细胞生成的影响。破骨细胞前体在不存在或存在破骨细胞生成增强剂M-CSF和RANKL的情况下进行培养，并进一步用代表吸烟者血浆和唾液中观察到的浓度的尼古丁水平进行处理。结果观察到，低浓度的尼古丁会引起破骨细胞分化增加，但只有在存在M-CSF和RANKL的情况下，它才能够显著提高破骨细胞的吸收能力。NFkB通路的轻微下调以及TNF-α尤其是PGE2的产生增加与尼古丁观察到的作用有关。在高浓度下，尼古丁显示出细胞毒性作用，导致细胞密度降低。总之，吸烟者血浆中发现的尼古丁水平能够直接作用于破骨细胞前体，诱导其破骨细胞分化。这种刺激行为似乎取决于前体细胞破骨细胞分化的阶段，这意味着，在不存在M-CSF和RANKL的情况下，它仅有利于破骨细胞分化的初始阶段，而在存在生长因子的情况下，它们的吸收能力也会显著增加。
