Disciplina de Histologia e Biologia Estrutural, Departamento de Morfologia e Genética, Escola Paulista de Medicina - EPM, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brasil.
Departamento de Ginecologia, Escola Paulista de Medicina - EPM, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brasil.
J Mol Histol. 2021 Apr;52(2):321-333. doi: 10.1007/s10735-020-09953-x. Epub 2021 Jan 6.
It is known that estrogen deficiency increases osteoclast formation and activity. Autophagy, a cell survival pathway, has been shown to be crucial for osteoclast function. However, little is known about the effects of estrogen depletion on osteoclast autophagy. Here, we evaluated the effects of estrogen deficiency in the immunoexpression of autophagy mediators in alveolar bone osteoclasts of ovariectomized rats. Twelve adult female rats were ovariectomized (OVX-group) or SHAM-operated (SHAM-group). After three weeks, the rats were euthanized and maxillary fragments containing alveolar bone of the first molars were processed for light microscopy or transmission electron microscopy (TEM). Paraffin-sections were subjected to the TRAP method (osteoclast marker) or to the immunohistochemical detections of beclin-1, LC3α, and p62 (autophagy mediators); araldite-sections were processed for TEM. The number of TRAP-positive osteoclasts and the number of immunolabeled-multinucleated cells (MNCs) along the alveolar bone surface of the first molar were computed. The number of TRAP-positive osteoclasts and the number of beclin-1-, LC3α- and p62-immunolabelled osteoclasts were significantly higher in OVX-group than the SHAM-group. MNCs were frequently located juxtaposed to Howship lacunae along the alveolar bone surface, indicating that these cells are osteoclasts. TEM revealed osteoclasts exhibiting autophagosomes. Our data indicate that autophagy plays an important role during estrogen deficiency-induced osteoclastogenesis. Thus, our results contribute to a better understanding on the role of autophagy on osteoclasts under estrogenic deficiency, and reinforce the idea that modulation of autophagy may be a useful tool to inhibit excessive oral bone resorption in post-menopausal women.
已知雌激素缺乏会增加破骨细胞的形成和活性。自噬是一种细胞存活途径,对于破骨细胞的功能至关重要。然而,关于雌激素耗竭对破骨细胞自噬的影响知之甚少。在这里,我们评估了雌激素缺乏对去卵巢大鼠牙槽骨破骨细胞自噬介体免疫表达的影响。将 12 只成年雌性大鼠去卵巢(OVX 组)或假手术(SHAM 组)。3 周后,处死大鼠,取出包含第一磨牙牙槽骨的上颌骨片段进行光镜或透射电镜(TEM)检查。石蜡切片进行 TRAP 法(破骨细胞标志物)或 beclin-1、LC3α 和 p62(自噬介体)的免疫组织化学检测;醛树脂切片进行 TEM。计算第一磨牙牙槽骨表面 TRAP 阳性破骨细胞数量和免疫标记多核细胞(MNC)数量。OVX 组 TRAP 阳性破骨细胞数量和 beclin-1、LC3α 和 p62 免疫标记破骨细胞数量明显高于 SHAM 组。MNC 常位于牙槽骨表面 Howship 陷窝旁,表明这些细胞是破骨细胞。TEM 显示破骨细胞有自噬体。我们的数据表明自噬在雌激素缺乏诱导的破骨细胞发生中起重要作用。因此,我们的结果有助于更好地理解自噬在雌激素缺乏下对破骨细胞的作用,并强化了调节自噬可能是抑制绝经后妇女口腔骨过度吸收的有用工具的观点。