Master Program in Clinical Dentistry, Positivo University, R Pedro Viriato Parigot de Souza, 5300, Campo Comprido, Curitiba, Paraná, 81280-330, Brazil.
Master Program in Biotechnology, Positivo University , 5300, R Pedro Viriato Parigot de Souza, Campo Comprido, Curitiba, 81280-330, Paraná, Brazil.
Clin Oral Investig. 2018 Jun;22(5):1959-1971. doi: 10.1007/s00784-017-2292-y. Epub 2017 Dec 2.
TGF-β1 is a cytokine that may induce both osteoneogenesis through Runx-2 or fibrosis via the transcription of α-smooth muscle actin (α-SMA). Because it has been previously known that alendronate increases the level of TGF-β1 and that under the usual condition of bone metabolism the estrogen may prevent the fibrotic effect of TGF-β1, the aim of this study was to evaluate if alendronate alters the cellular differentiation process post calvarial surgery in estrogen-deficient specimens.
A transosseous defect that was 5 mm in diameter was created on the calvarium of each of 32 female rats with previous ovarian-salpingo-oophorectomy. All defects were treated with autografts, and 16 rats received the administration of 1 mg/kg of alendronate three times a week until euthanasia on the 15th and 60th day post surgery. Histomorphometric and immunohistochemical analyses of the expression of TGF-β1, estrogen receptor alpha nuclear (α-ER), α-SMA, BMPR1B, and Runx-2 were performed, and ELISA was used to measure the level of estrogen.
All animals demonstrated low levels of estrogen post ovarian-salpingo-oophorectomy. The histological results demonstrated larger bone matrix deposition in specimens treated with alendronate on the 15th day post surgery. The result was associated with a higher co-expression of TGF-β1, BMPR1B, and Runx-2 when compared with the control group. In addition, on the 60th day post surgery, the increase of bone matrix deposition from 15th to 60th day was discrete in specimens treated with alendronate compared with the control group. This result coincided with the intense simultaneous expression of TGF-β1, α-ER, and α-SMA, whereas the expression of BMPR1B and Runx-2 decreased.
The prolonged administration of alendronate altered the cranial repair in ovarian-salpingo-oophorectomized specimens due to the simultaneous occurrence of low estrogen and the presence of TGF-β1+/α-ER+ inducing the presence of α-SMA, whereas BMPR1B and Runx-2 were suppressed.
The prolonged administration of alendronate alters osteoneogenesis and induces an unusual microenvironment in the bone that seems to imitate the physiological tissue damage that culminates in the loss of the functional layer of endometrium.
TGF-β1 是一种细胞因子，它可以通过 Runx-2 诱导成骨作用，也可以通过转录 α-平滑肌肌动蛋白（α-SMA）诱导纤维化。由于先前已知阿仑膦酸钠会增加 TGF-β1 的水平，而在骨代谢的正常情况下，雌激素可以防止 TGF-β1 的纤维化作用，因此本研究的目的是评估阿仑膦酸钠是否会改变去卵巢大鼠颅骨手术后的细胞分化过程。
32 只雌性大鼠行卵巢-输卵管-卵巢切除术，在颅骨上制作直径为 5mm 的穿骨缺损。所有缺损均用自体移植物治疗，16 只大鼠每周接受 1mg/kg 阿仑膦酸钠 3 次治疗，直至术后 15 天和 60 天安乐死。对 TGF-β1、雌激素受体 α 核（α-ER）、α-SMA、BMPR1B 和 Runx-2 的表达进行组织形态计量学和免疫组织化学分析，并使用 ELISA 测量雌激素水平。
所有动物去卵巢-输卵管-卵巢切除术后雌激素水平均较低。组织学结果显示，术后 15 天用阿仑膦酸钠治疗的标本中骨基质沉积更大。与对照组相比，这与 TGF-β1、BMPR1B 和 Runx-2 的共表达增加有关。此外，术后 60 天，与对照组相比，阿仑膦酸钠治疗组从第 15 天到第 60 天的骨基质沉积增加不明显。这一结果与 TGF-β1、α-ER 和 α-SMA 的同时强烈表达一致，而 BMPR1B 和 Runx-2 的表达减少。
长期使用阿仑膦酸钠改变了去卵巢大鼠颅骨修复的方式，原因是同时存在低雌激素和 TGF-β1+/α-ER+，导致 α-SMA 的存在，而 BMPR1B 和 Runx-2 则受到抑制。
长期使用阿仑膦酸钠会改变成骨作用，并在骨骼中产生一种异常的微环境，这种微环境似乎模仿了导致功能性子宫内膜层丧失的生理性组织损伤。
